Offspring Immunity Research Articles

Maternal Immunity and Immune Improvement of Koi Cyprinus rubrofuscus Larvae after DNA Vaccine against Hoi Herpesvirus

Vaccination is an efficient step in preventing disease caused by koi herpesvirus in koi fish (Cyprinus rubrofuscus). This study aimed to investigates the impact of maternal broodstock vaccination with ORF81 DNA vaccine on the transmission of maternal immunity to offspring against KHV. The ORF81 DNA vaccine has been shown to increase RPS, but its effect on maternal immunity in koi offspring after vaccination has not been evaluated. The study examined koi broodstocks vaccinated with the ORF81 DNA vaccine 45 and 60 days before spawning (45V and 60V) at a dose of 12.5 μg/100 g. Immunological parameters were assessed in broodstock, eggs, and larvae. Immune gene expression was also analyzed using the qPCR method. The results showed that lysozyme activity and antibody levels in eggs from vaccinated mothers were higher, though not significantly different. Meanwhile, lysozyme activity and antibody levels in mothers were significantly higher (p<0.05) compared to controls. Immunoglobulin-M gene (IgM) and recombination-activating gene 1 (RAG1), were significantly induced. The relative survival percentage increased significantly in larvae produced from broodstocks with 60V. These findings indicate that broodstocks treated with the ORF81 DNA vaccine can enhance the immune response of their offspring.

Maternal Helminth Infection Causes Dysfunctional B Cell Development in Male Offspring.

Infections during pregnancy are known to trigger alterations in offspring immunity, often leading to increased disease susceptibility. Maternal helminth infections correlate with lower Ab titers to certain childhood immunizations and putative decreased vaccine efficacy. The mechanisms that underlie how maternal infection blunts offspring humoral responses are unclear. Using our murine model of maternal schistosomiasis, we found that maternal helminth infection decreases the germinal center response of all offspring to tetanus immunization. However, only male offspring have defects in memory B cell and long-lived plasma cell generation. We found this sex-specific aberration begins during B cell development within the bone marrow via alteration of the IL-7 niche and persists throughout antigenic activation in the germinal center in the periphery. Critically, these defects in males are cell intrinsic, persisting following adoptive transfer to control male pups. Together, these data show that maternal infections can alter both the bone marrow microenvironment and the development of B lymphocytes in a sex-specific manner. This study correlates maternal infection induced defects in early life B cell development with ineffective Ab responses after vaccination.

Maternal gastrointestinal nematode infection alters hippocampal neuroimmunity, promotes synaptic plasticity, and improves resistance to direct infection in offspring

The developing brain is vulnerable to maternal bacterial and viral infections which induce strong inflammatory responses in the mother that are mimicked in the offspring brain, resulting in irreversible neurodevelopmental defects, and associated cognitive and behavioural impairments. In contrast, infection during pregnancy and lactation with the immunoregulatory murine intestinal nematode, Heligmosomoides bakeri, upregulates expression of genes associated with long-term potentiation (LTP) of synaptic networks in the brain of neonatal uninfected offspring, and enhances spatial memory in uninfected juvenile offspring. As the hippocampus is involved in spatial navigation and sensitive to immune events during development, here we assessed hippocampal gene expression, LTP, and neuroimmunity in 3-week-old uninfected offspring born to H. bakeri infected mothers. Further, as maternal immunity shapes the developing immune system, we assessed the impact of maternal H. bakeri infection on the ability of offspring to resist direct infection. In response to maternal infection, we found an enhanced propensity to induce LTP at Schaffer collateral synapses, consistent with RNA-seq data indicating accelerated development of glutamatergic synapses in uninfected offspring, relative to those from uninfected mothers. Hippocampal RNA-seq analysis of offspring of infected mothers revealed increased expression of genes associated with neurogenesis, gliogenesis, and myelination. Furthermore, maternal infection improved resistance to direct infection of H. bakeri in offspring, correlated with transfer of parasite-specific IgG1 to their serum. Hippocampal immunohistochemistry and gene expression suggest Th2/Treg biased neuroimmunity in offspring, recapitulating peripheral immunoregulation of H. bakeri infected mothers. These findings indicate maternal H. bakeri infection during pregnancy and lactation alters peripheral and neural immunity in uninfected offspring, in a manner that accelerates neural maturation to promote hippocampal LTP, and upregulates the expression of genes associated with neurogenesis, gliogenesis, and myelination.

Maternal Infection and altered fetal immune programming.

Abstract The maternal-fetal interface involves complex and balanced interactions between mother and fetus, which support the development of the fetal immune system. While we know maternal helminth infection during pregnancy is known to disrupt this relationship and affect neonatal immune development, the fundamental mechanisms that drive fetal immune programming is not completely understood. To further examine how maternal parasitic infection influences offspring immunity, we established a model in which female mice prior to mating are infected with the persistent mouse intestinal helminth, Heligmosomoides polygyrus (HP). One week after infection, female mice are mated, and the progeny are aged to adulthood. The offspring are then challenged with influenza virus. Intriguingly, we found that offspring born from mothers with HP infections were less susceptible to influenza challenge than offspring born from uninfected mothers. This data implies that the effects of maternal helminth infection are long lasting, and potentially involve fetal programming during the early development of the immune system.

Susceptibility, Immunity, and Persistent Infection Drive Endemic Cycles of Coxiellosis on Dairy Farms.

Coxiella (C.) burnetii, a zoonotic bacterium, is prevalent in dairy farms. Some cows develop a persistent infection and shed C. burnetii into milk and occasionally by amniotic fluid at calving. Serological diagnosis of Q fever in humans is performed by phase (Ph)-specific antibody tests; PhII antibodies usually indicate an acute infection, while the development of a chronic infection is characterised by elevated PhI antibody titres. Phase-specific tests have now been established for diagnosis of coxiellosis in cattle. Additionally, an interferon-γ (IFN-γ) recall assay has been implemented to assess cellular immunity to C. burnetii in cattle. Milk samples from all lactating cows (n = 2718) of 49 Bavarian dairy farms were collected through a convenience sample and analysed for phase-specific antibodies. Antibody profiles were evaluated by age. Based on the seropositivity of first-lactation cows, three distinct herd profiles were observed: an 'acute' state of herd infection was characterised by a PhI-/PhII+ pattern. The detection of PhI antibodies (PhI+/PhII+) characterised the 'chronic' state, and seronegative results defined the 'silent' state of herd infection. If antibodies had not been detected in multiparous cows, the herd was considered as probably free of coxiellosis. The analysed cattle herds were noted to have an 'acute' (n = 12, 24.5%), 'chronic' (n = 18, 36.8%), or 'silent' state of herd infection (n = 16, 32.6%). Only three farms (6.1%) were classified as 'free' of C. burnetii. The detection of these herd states over a time period of 4 years in one farm indicated that the described states occur in a cyclical manner. Frequently, a wave-like profile was seen, i.e., a circumscribed seronegative age group was flanked by seropositive age groups. In seronegative animals, IFN-γ reactivity was demonstrated. Seroconversion after vaccination was observed by day 7 post-vaccination in chronically infected herds, whereas in the case of silent infection, it started by day 14. These data indicated a pre-existing immunity in seronegative animals in chronically infected herds. Additionally, IFN-γ reactivity was detected in seronegative calves (>3 months) and heifers from chronically infected farms compared to a negative farm. An infection prior to 3 months of age resulted in cellular immunity in the absence of detectable antibodies. An infection around calving would explain this. The aforementioned circumscribed seronegative age groups are, therefore, explained by an infection early in life during active shedding at calving. Based on these results, an endemic cycle of coxiellosis is proposed: Susceptible young heifers get infected by persistently infected cows. Subsequently, shedding of C. burnetii at calving results in infection and then in cellular immunity in offspring. When these calves enter the cow herd two years later, a maximum of herd immunity is achieved, shedding ceases, and new susceptible animals are raised. In an acutely infected dairy farm, the PhI+/PhII+ serological pattern prevailed in second-lactation cows. In this study, stored sera collected since birth were analysed retrospectively. From the earliest seroconversion, the peak of seroconversion took about 33 months. These data suggested a slow spread of infection within herds. The classification of dairy cow herds is a promising basis for further analysis of the clinical impact of coxiellosis.

Maternal-driven immune education in offspring.

Maternal environmental exposures, particularly during gestation and lactation, significantly influence the immunological development and long-term immunity of offspring. Mammalian immune systems develop through crucial inputs from the environment, beginning in utero and continuing after birth. These critical developmental windows are essential for proper immune system development and, once closed, may not be reopened. This review focuses on the mechanisms by which maternal exposures, particularly to pathogens, diet, and microbiota, impact offspring immunity. Mechanisms driving maternal-offspring immune crosstalk include transfer of maternal antibodies, changes in the maternal microbiome and microbiota-derived metabolites, and transfer of immune cells and cytokines via the placenta and breastfeeding. We further discuss the role of transient maternal infections, which are common during pregnancy, in providing tissue-specific immune education to offspring. We propose a "maternal-driven immune education" hypothesis, which suggests that offspring can use maternal encounters that occur during a critical developmental window to develop optimal immune fitness against infection and inflammation.

Prenatal Inflammation Promotes Enhanced Allergic Lung Inflammation By Programming Hyperactive ILC2s from Fetal Hematopoietic Progenitors

Our lab has recently demonstrated that prenatal inflammation, induced by maternal immune activation via viral-mimetic poly(I:C), specifically activates and expands lymphoid-biased developmentally-restricted hematopoietic stem cells (drHSCs) in the fetal liver, resulting in the generation of hyperactivated innate-like B1-B cells in the postnatal period that produce greater levels of IgM, IgG3, and IL-10 on a per-cell basis. We hypothesize that dysregulation and hyperactivation of long-lived fetal-derived innate immune compartments that persist across the lifespan underlies disease susceptibility into adulthood. Here we elucidate a mechanism by which prenatal inflammation imparts persistent changes to lung immunity and function by programming innate lymphoid cell output from fetal hematopoietic progenitors, resulting in adverse responses to allergen challenge into adulthood. To investigate how prenatal inflammation impacted fetal- and neonatal-derived group-2 innate lymphoid cells (ILC2s), we profiled changes to ILC2 establishment across early postnatal life. In response to prenatal inflammation, ILC2s were significantly expanded at postnatal day (P)9 and remained robustly expanded through adulthood, while also exhibiting a greater proliferation capacity through their peak expansion period postnatally (P14). At P14, prenatal inflammation also robustly increased IL-5 and IL-13 production from ILC2s after ex-vivo stimulation, concomitant with higher expression of killer cell lectin-like receptor G1 (KLRG1), indicative of an enhanced activation state. To determine hematopoietic origins of expanded and hyperactive ILC2s, we profiled changes to an immediate upstream precursor of the ILC lineage within the neonatal bone marrow (BM) and fetal liver after prenatal inflammation. At P14, prenatal inflammation did not alter the establishment of BM common helper-like innate lymphoid progenitors (CHILPs), whereas fetal liver CHILPs were robustly expanded by both cellularity and frequency at embryonic day (E)15.5 and E17.5 compared to saline treated controls. To test if the changes observed in mature ILC2s and their immediate precursors could be programmed at the stem cell level, we transplanted fetal liver drHSCs one day post-poly(I:C) or saline into irradiated adult recipients. One month post-transplantation, donor-derived ILC2s from the prenatal-inflammation condition produced more IL-13 cytokine within the lung microenvironment compared to saline controls, demonstrating that prenatal inflammation programs fetal hematopoietic precursors during development to generate hyperactive ILC2s. Single-cell RNA sequencing of over 26,000 lung ILC2s at P14 revealed extensive heterogeneity in response to prenatal inflammation. Unsupervised clustering analysis identified clusters unique to prenatal inflammation conditions, with transcriptional profiles significantly overlapping with ILC2 signatures identified in models of allergic airway inflammation (AAI). As prenatal inflammation induced functional and transcriptional shifts in ILC2s that regulate lung immunity, we profiled changes to the developing lung immune landscape in response ILC2 hyperactivation. ILC2 expansion and hyperactivation was concomitant with remodeling of multiple lung immune compartments, including expanded B-cells, T-cells, and eosinophils at P14. We acutely challenged mice intranasally with papain allergen to determine if prenatal inflammation modulated lung innate immune responses. ILC2s and eosinophils expanded in response to papain challenge and exhibited even greater expansion under prenatal inflammation conditions. As eosinophilia is a hallmark feature of AAI, we assessed respiratory mechanics using the FlexiVent system in adult mice to measure the underlying impact of prenatal inflammation on lung function in the context of acute allergen challenge. Exposure to prenatal inflammation alone caused a decrease in lung compliance and pressure-volume loops, indicative of pulmonary morbidity, that was further exacerbated by papain challenge compared to saline treated controls. Together, our data reveal a mechanism by which prenatal inflammation can program hyperactivity of ILC2s at the fetal HSC-level during embryonic development, resulting in lasting changes to postnatal lung immunity and lung disease susceptibility in offspring.

N-3 Polyunsaturated Fatty Acids as a Nutritional Support of the Reproductive and Immune System of Cattle-A Review.

This paper focuses on the role of n-3 fatty acids as a nutrient crucial to the proper functioning of reproductive and immune systems in cattle. Emphasis was placed on the connection between maternal and offspring immunity. The summarized results confirm the importance and beneficial effect of n-3 family fatty acids on ruminant organisms. Meanwhile, dietary n-3 fatty acids supplementation, especially during the critical first week for dairy cows experiencing their peripartum period, in general, is expected to enhance reproductive performance, and the impact of its supplementation appears to be dependent on body condition scores of cows during the drying period, the severity of the negative energy balance, and the amount of fat in the basic feed ration. An unbalanced, insufficient, or excessive fatty acid supplementation of cows' diets in the early stages of pregnancy (during fetus development) may affect both the metabolic and nutritional programming of the offspring. The presence of the polyunsaturated fatty acids of the n-3 family in the calves' ration affects not only the performance of calves but also the immune response, antioxidant status, and overall metabolism of the future adult cow.

Вплив перенесених паразитарних інфекцій під час вагітності на імунну систему плода (огляд літератури)

Transmission of infections during pregnancy is known to alter the development and functioning of the fetus immune system, resulting in an inadequate immune response to common childhood infections and immunizations. Although it is a developing and actively researched topic, maternal parasitic infections remain poorly understood. Millions of women of reproductive age are currently at risk of parasite infection, while many pregnant, chronically infected women are excluded from mass drug administration due in part to a lack of resources, as well as fear of unknown adverse fetal outcomes. infection, there is no clear mechanism for understanding how maternal infection reprograms offspring immunity. Purpose - to determine the currently studied mechanisms of the influence of parasitic infections transmitted during pregnancy on the immune system of the fetus and to describe the possible effects of these influence in the long term on the health of children. Conclusions. The study of maternal parasitic infections is a rapidly developing field. Although infant mortality rates are declining, areas with endemic parasites still have the highest infant mortality rates. As antiparasitic therapy is not always curable, there is a critical need to understand the effects of maternal infection on offspring immune development. Due to the increased risk of immune alteration due to maternal inflammation and reduced passive antibody transmission, maternal parasitic infections and their mechanism of adverse immunomodulation must be uncovered to improve vaccination regimens and reduce childhood morbidity in endemic regions. No conflict of interests was declared by the author.

Maternal polysorbate 80 exposure causes intestinal ILCs and CD4+ T cell developmental abnormalities in mouse offspring

This study aimed to investigate the transgenerational impacts of maternal intake of polysorbate 80 (P80), an emulsifier widely used in modern society, on the development of offspring immunity. Our results revealed that maternal P80 treatment led to impaired differentiation of innate lymphoid cells (ILCs) and CD4+ T cells in the small intestinal lamina propria (SiLP), resulting in intestinal dyshomeostasis in female offspring. Furthermore, we found that SiLP ILCs abundances were significantly altered in 0-day-old fetuses from P80-treated mothers, indicating a prenatal impact of P80-treated mothers on offspring immunity. Additionally, cesarean section and foster-nursing studies demonstrated that P80-induced altered SiLP ILCs in 0-day-old fetuses could further induce dysregulation of ILCs and CD4+ T cells in the SiLP, thus promoting intestinal dysregulation in offspring later in life. Overall, our findings suggest that maternal P80 intake could prenatally program the development of offspring immunity, exerting a significant and long-lasting impact.

Influenza A virus infection during pregnancy causes immunological changes in gut-associated lymphoid tissues of offspring mice.

Maternal influenza A virus (IAV) infection during pregnancy can affect offspring immune programming and development. Offspring born from influenza-infected mothers are at increased risk of neurodevelopmental disorders and have impaired respiratory mucosal immunity against pathogens. The gut-associated lymphoid tissue (GALT) represents a large proportion of the immune system in the body and plays an important role in gastrointestinal (GI) homeostasis. This includes immune modulation to antigens derived from food or microbes, gut microbiota composition, and gut-brain axis signaling. Therefore, in this study, we investigated the effect of maternal IAV infection on mucosal immunity of the GI tract in the offspring. There were no major anatomical changes to the gastrointestinal tract of offspring born to influenza-infected dams. In contrast, maternal IAV did affect the mucosal immunity of offspring, showing regional differences in immune cell profiles within distinct GALT. Neutrophils, monocytes/macrophages, CD4+ and CD8+ T cells infiltration was increased in the cecal patch offspring from IAV-infected dams. In the Peyer's patches, only activated CD4+ T cells were increased in IAV offspring. IL-6 gene expression was also elevated in the cecal patch but not in the Peyer's patches of IAV offspring. These findings suggest that maternal IAV infection perturbs homeostatic mucosal immunity in the offspring gastrointestinal tract. This could have profound ramifications on the gut-brain axis and mucosal immunity in the lungs leading to increased susceptibility to respiratory infections and neurological disorders in the offspring later in life.NEW & NOTEWORTHY Influenza A virus (IAV) infection during pregnancy is associated with changes in gut-associated lymphoid tissue (GALT) in the offspring in a region-dependent manner. Neutrophils and monocytes/macrophages were elevated in the cecal patch of offspring from infected dams. This increase in innate immune cell infiltration was not observed in the Peyer's patches. T cells were also elevated in the cecal patch but not in the Peyer's patches.

Dynamics of lymphoid-mammary epithelial cell interaction during pregnancy and lactation

Abstract Breast milk has been shown to play a key role in the transfer of immunity from mother to offspring. Antibodies and lymphoid cells can be passed through breast milk and impact offspring immunity. However, the role of these lymphoid cells in lactation and in the control of offspring immunity remains unclear. We observed that the lymphoid cells present in the breast milk are distinct from those found in the blood. Compared to the blood, breast milk T cells are enriched in a T-bet +unconventional population. Imaging analysis revealed that these T-bet +cells gradually accumulate in the mammary gland during pregnancy and are specifically localized around and inside the mammary epithelium. We will utilize confocal and intravital imaging of the mammary gland in virgin, pregnant, and lactating mice to characterize the dynamics of this mammary-associated T-bet +population throughout pregnancy and lactation. Understanding the dynamics of T-bet +cells and their anatomical localization within the mammary gland will help us decode how these cells impact the remodeling of the mammary epithelium during pregnancy and lactation. We propose that the remodeling of the mammary gland imparted by the immune system can also influence the transfer of immunity from mother to offspring, thereby affecting the development of offspring immunity. This work was supported in part by intramural funds of NIAID, NIH.

Dynamics of immune cells in the fetal brain upon viral inflammation

Abstract The fetal immune system undergoes many developmental milestones, with several immune cell subsets emerging during pregnancy. Recent evidence has shown that maternal infections during pregnancy can influence offspring immunity in the long term. Moreover, maternal infections are associated with an increased risk for neurodevelopmental disorders in the offspring. Yet, our knowledge of the immune cell dynamics in the fetal brain throughout gestation and their response to inflammation remains limited. We sought to characterize the phenotype of immune cells in murine implantation sites at mid-gestation, a time point equivalent to the beginning of the second trimester in humans. Our preliminary studies revealed specific and robust populations of maternal and fetal immune cells in murine fetal brains. Quite unexpectedly, one of these populations expressed NK1.1, a marker for natural killer cells and innate lymphoid cells. Given that the presence of maternal and fetal NK1.1+ cells in the fetal brains at mid-gestation has not been previously reported, our goal is to determine the phenotype and kinetics of the maternal and fetal NK1.1+ immune cells in the fetal brain during a healthy pregnancy and upon congenital infection.To address this, I will use a high-dimensional sequencing technology, CITE-seq, that allows me to simultaneously study surface markers and gene expression of cells. Maternal immune responses critically impact fetal development during gestation and have long-term health outcomes in offspring. Understanding maternal and fetal immune responses to inflammation will inform the origin of fetal inflammation-driven neurodevelopmental disorders and ultimately improve offspring’s health outcomes. Supported by Packard Foundation Fellowship for Science and Engineering

Developmental immunotoxicity of maternal exposure to yttrium nitrate on BALB/c offspring mice.

Yttrium is a typical heavy rare earth element with widespread use in numerous sectors. Only one previous study has indicated that yttrium has the potential to cause developmental immunotoxicity (DIT). Therefore, there remains a paucity of evidence on the DIT of yttrium. This study aimed to explore the DIT of yttrium nitrate (YN) and the self-recovery of YN-induced DIT. Dams were treated with 0, 0.2, 2, and 20 mg/kg bw/day YN by gavage during gestation and lactation. No significant changes were found in innate immunity between the control and YN-treated groups in offspring. In female offspring at postnatal day 21 (PND21), YN markedly inhibited humoral and cellular immune responses, the proliferative capacity of splenic T lymphocytes, and the expression of costimulatory molecules in splenic lymphocytes. Moreover, the inhibitory effect on cellular immunity in female offspring persisted to PND42. Unlike females, YN exposure did not change the adaptive immune responses in male offspring. Overall, maternal exposure to YN showed a strong DIT to offspring, with the lowest effective dose of 0.2 mg/kg in the current study. The toxicity of cellular immunity could persist throughout development into adulthood. There were sex-specific differences in YN-induced DIT, with females being more vulnerable.

Maternal tributyrin supplementation in late pregnancy and lactation improves offspring immunity, gut microbiota, and diarrhea rate in a sow model.

Several studies have evaluated the effects of tributyrin on sow reproductive performance; however, none of these studies have investigated the effects of tributyrin on sow gut microbiota and its potential interactions with immune systems and milk composition. Therefore, we speculated that tributyrin, the combination of butyrate and mono-butyrin without odor, would reach the hindgut and affect the intestinal microbiota composition and play a better role in regulating sow reproductive performance, gut flora, and health. Thirty sows (Landrace × Yorkshire) were randomly divided into two groups: the control group (CON) and the tributyrin group (TB), which received basal diet supplemented with 0.05% tributyrin. The experimental period lasted for 35 days from late pregnancy to lactation. The results showed that TB supplementation significantly shortened the total parturition time and reduced the diarrhea rate in suckling piglets. On day 20 of lactation, the milk fat and protein levels increased by 9 and 4%, respectively. TB supplementation significantly improved the digestibility of dry material, gross energy, and crude fat in the sow diet, but had no significant effect on crude protein digestibility. Furthermore, TB supplementation increased the levels of IL-10, IL-6, and IgA in the blood of weaned piglets, but had no effect on maternal immunity. Analysis of the fecal microbial composition revealed that the addition of TB during late gestation and lactation increased the microbiota diversity in sows and piglets. At the phylum level, sows in the TB group had a slight increase in the relative abundance of Bacteroidota and Spirochaetota and a decrease in Firmicutes. At the order level, the relative abundance of Lactobacillales was increased in piglets and sows, and the TB group showed increased relative abundance of Enterobacterales and significantly decreased relative abundance of Oscillospirales in piglets. At family level, the relative abundance of Lactobacillaceae, Oscillospiraceae, and Christensenellaceae increased in sows, and the relative abundance of Enterobacteriaceae and Lactobacillaceae increased in piglets. At genus level, the relative abundance of Lactobacillus increased in sows and piglets, but the relative abundance of Subdoligranulum and Eubacterium_fissicatena_group decreased in piglets in the TB group. In conclusion, tributyrin supplementation shortened the farrowing duration and reduced the diarrhea rate of piglets by improving the inflammatory response and composition of gut microbiota in piglets and sows.

Maternal helminth infection protects offspring from high-fat-diet-induced obesity through altered microbiota and SCFAs.

Helminth-induced Th2 immunity and gut microbiota have been recently shown to be highly effective in modulating metabolic syndromes in animal models. This study aimed to determine whether maternal immunity and microbial factors affect the induction and development of obesity in offspring. Here, Heligomosomoides polygyrus (Hp)-infected or control female C57BL/6J mice mated with normal males and their offspring were fed a high-fat diet (HFD) for 9 weeks after weaning. Our results showed that Hp-induced maternal outcomes during gestation and lactation significantly impacted offspring metabolic phenotypes. This was evidenced by results showing that offspring from helminth-infected mothers on an HFD (Hp-offspring + HFD) gained significantly less body weight than those from uninfected mothers (Cont-offspring + HFD). Hp-offspring + HFD exhibited no Th2 phenotype but displayed a pattern of gut microbiota composition similar to that of Hp-infected mothers. Cross-fostering experiments confirmed that the helminth-induced maternal attenuation of offspring obesity was mediated through both prenatal and postnatal effects. Our results further showed that helminth-infected dams and their offspring had a markedly altered gut microbiome composition, with increased production of short-chain fatty acids (SCFAs). Intriguingly, Hp-infected mothers and Hp-offspring + HFD showed increased SCFA receptor (GPR) expression in adipose and colonic tissues compared to noninfected mothers and Cont-offspring + HFD, respectively. Moreover, SCFA supplementation to the pups of uninfected control mothers during lactation protected against HFD-induced weight gain, which corresponded with changes in gut bacterial colonization. Collectively, our findings provide new insights into the complex interaction of maternal immune status and gut microbiome, Hp infection, and the immunity and gut microbiome in obese-prone offspring in infant life.

Maternal γδ Tcells shape offspring pulmonary type 2 immunity in a microbiota-dependent manner.

Immune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ Tcell-deficient (TCRδ-/-) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared with the progeny of γδ Tcell-sufficient dams. Upon helminth infection, mice born from TCRδ-/- dams sustain an increased type 2 inflammatory response. This is independent of the genotype of the pups. Instead, the offspring of TCRδ-/- dams harbors a distinct intestinal microbiota, acquired during birth and fostering, and decreased levels of intestinal short-chain fatty acids (SCFAs), such as pentanoate and hexanoate. Importantly, exogenous SCFA supplementation inhibits type 2 innate lymphoid cell function and suppresses first-breath- and infection-induced inflammation. Taken together, our findings unravel a maternal γδ Tcell-microbiota-SCFA axis regulating neonatal lung immunity.

Effects of yeast-derived postbiotic supplementation in late gestation and lactation diets on performance, milk quality, and immune function in lactating sows.

This experiment was conducted to determine the effects of yeast-derived postbiotic (YDP) supplementation in sow diets during late gestation and lactation on the performance of sows and their offspring. At 90-d gestation, 150 sows (Landrace × Large White, parity: 3.93 ± 0.11) were allocated to three dietary treatments (n = 50 per treatment): 1) basal diet (control [CON]), 2) basal diet with 1.25 g/kg YDP (0.125 group), and 3) basal diet with 2.00 g/kg YDP (0.200 group). The experiment continued until the end of weaning (day 21 of lactation). Supplementation with YDP resulted in greater deposition of backfat in sows during late gestation and an increasing trend in average weaning weight of piglets than observed in the CON group (P < 0.01, P = 0.05). Supplementation with YDP decreased piglet mortality and diarrhea index in piglets (P < 0.05). In farrowing sows' serum, the glutathione peroxide content in the YDP group was lower than that in the CON group (P < 0.05); the content of immunoglobulin A (IgA) in the 0.200 group or YDP group was higher than that in the CON group (P < 0.05). In lactating sows' serum, malondialdehyde content was higher in the YDP group (P < 0.05). In day 3 milk of sows, the 0.200 group tended to increase the lactose content (P = 0.07), and tended to decrease the secretory immunoglobulin A (sIgA) content (P = 0.06) with respect to that in the CON group. The sIgA content in the YDP group was lower than that in the CON group (P < 0.05). In the milk of sows, the 0.200 group tended to increase the lactose content with respect to that in the CON group (P = 0.08); the immunoglobulin G (IgG) content in the 0.125 group or YDP group was higher than that in the CON group (P < 0.05). YDP supplementation increased the IgA content in the milk (P < 0.01). In sow placenta, the content of total anti-oxidant capacity in the YDP group was higher than that in the CON group (P = 0.05); and the content of transforming growth factor-β in the YDP group was higher than that in the CON group (P < 0.05). In piglet serum, the content of IgG and immunoglobulin M in the 0.125 group was higher than that in the CON and 0.200 groups (P < 0.05). In summary, this study indicated that feeding sows diets supplemented with YDP from late gestation through lactation increased sows' backfat deposition in late gestation and piglets' weaning weight; decreased piglet mortality and diarrhea index in piglets; and improved maternal and offspring immunity.

Serotonin-1A receptor, a psychiatric disease risk factor, influences offspring immunity via sex-dependent genetic nurture.

Serotonin-1A receptor (5HT1AR) is highly expressed in corticolimbic regions and its deficit is associated with anxiety and depression. A similar reduction in 5HT1AR heterozygous knockout (Het) mice results in anxiety-like and increased stress-reactivity phenotypes. Here we describe immunological abnormalities in Het females, characterized by an activated state of innate and adaptive immune cells. Het males showed only limited immune dysregulation. Similar immune abnormalities were present in the genetically WT female (F1) but not male offspring of Het mothers, indicating sex-specific immune system abnormalities that are dependent on the mother's 5HT1AR deficit, known as maternal genetic effect or "genetic nurture". Expression profiling of the maternal-fetal interface revealed reduced immune cell invasion to decidua and accelerated trophoblast migration. These data suggest that 5HT1AR deficit, by altering the maternal immune system and midgestational in utero environment, leads to sex-biased outcomes, predominantly immune dysregulation in the female and anxiety-like behavior in the male offspring.

Effects of maternal choline supplementation on performance and immunity of progeny from birth to weaning.

The objectives were to investigate whether supplementation with rumen-protected choline (RPC) during late pregnancy in Holstein cows affects offspring immunity and growth, and whether effects are utero-placental, colostrum dependent, or both. A total of 105 multiparous Holstein cows were assigned randomly to a prepartum diet (1.54 Mcal of NEL/kg of DM, and 15.8% CP) without (control) or with added RPC (12.9 g/d of choline ion). Calves (n = 111) were blocked by sex and assigned randomly to colostrum from control cows or colostrum from RPC cows, resulting in 4 treatments in a 2 × 2 factorial arrangement: (1) calves born and fed colostrum from non-supplemented dams (NN; n = 33); (2) calves from non-supplemented dams and fed colostrum from RPC-fed cows (NC; n = 25); (3) calves from RPC-supplemented dams and colostrum from non-supplemented cows (CN; n = 28); and (4) calves from RPC-supplemented dams and colostrum from RPC-fed cows (CC; n = 25). Growth, intakes, and immunity of females were evaluated up to 56 d of age. Growth and intake of male calves was evaluated up to 35 d of age, and physiological and immune responses to intravenous LPS challenge were evaluated from 21 to 35 d of age. Effects of prenatal and colostrum treatments and interactions between treatments were analyzed using mixed models. Calves fed colostrum from RPC-supplemented dams had a 17.4% increase in apparent efficiency of absorption of IgG compared with calves fed colostrum from control dams (27.4 vs. 23.3%). Incidence of fever in the first 21 d of age tended to be less in females born from RPC-supplemented dams compared with females born from control dams (31 vs. 58%). Prenatal RPC females had increased hematocrit and concentrations of red blood cells, leukocytes, neutrophils, and lymphocytes in blood compared with prenatal females born from control dams. Compared with prenatal control females, prenatal RPC females had greater intake of milk replacer (704 vs. 748 ± 9.9 g/d) and starter (45.4 vs. 60.2 ± 5.9 g/d) during the first 21 d of age. In male calves, mean intake of DM was greater (1,074 vs. 976 ± 45 g/d) after the LPS challenge (0 to 8 d) by calves born from dams fed RPC compared with males born from control dams. Calves born from RPC-fed dams also had lower mean rectal temperature (39.0 vs. 39.2°C) and mean respiration rate (35.6 vs. 39.3 breaths/min) compared with males born from control dams. Moreover, serum concentrations of metabolites (i.e., β-hydroxybutyric acid, fatty acids, and glucose), cytokines (i.e., tumor necrosis factor-α) and acute phase proteins (i.e., serum amyloid A) were consistent with less-severe inflammatory response to LPS in males born from dams fed RPC compared with control. Source of colostrum and interaction between prenatal and colostrum treatments had minimal effects on calf responses to LPS. Overall, maternal RPC supplementation during late gestation suggests a positive effect on immunity, in that colostrum from RPC-fed dams increased efficiency of IgG absorption and maternal supplementation with RPC during late gestation, regardless of colostrum source, attenuated responses to LPS.