Development Of Immune System Research Articles

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.

UBE2N Is Essential for Maintenance of Skin Homeostasis and Suppression of Inflammation

UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models that deleted Ube2n in skin cells in a temporally and spatially controlled manner. We found that Ube2n-knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included inflammation, epidermal and dermal thickening, parakeratosis, and increased immune cell infiltration, as well as signs of edema and blistering. Single cell transcriptomic analyses and RT-qPCR showed that Ube2n KO keratinocytes expressed elevated myeloid cell chemo-attractants such as Cxcl1 and Cxcl2 and decreased the homeostatic T lymphocyte chemo-attractant Ccl27a. Consistently, the infiltrating immune cells were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that expressed high levels of inflammatory cytokines such as Il1β and Il24. Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated inflammation, epidermal and dermal thickening, and immune infiltration of the Ube2n mutant skin. Together, these findings highlight a key role of keratinocyte-UBE2N in maintenance of epidermal homeostasis and skin immunity, and identify IRAK1/4 as potential therapeutic target for inflammatory skin disorders.

Association of dietary quality during pregnancy with fetal immune function in Guangzhou

To investigate the situation of women's dietary quality during pregnancy and explore the correlations between maternal dietary index and fetal immune function. From September 2010 to February 2011, pregnant women who had routine physical examination in Yuexiu District and Baiyun District Maternal and Child Health Hospital of Guangzhou were recruited as study objects to use 3-day 24-hour dietary review to investigate diet during pregnancy, and general demographic information of pregnant women was collected through questionnaire, and the neonatal umbilical cord blood was collected during delivery. Laboratory detection of immunological indicators included IgG, IgA, IgM, IFN-γ and IL-6. The quality of diet during pregnancy was evaluated by diet quality index for pregnancy(DQI-P), dietary balance index for pregnancy(DBI-P) and alternate Medierranean diet score(aMED). Spearman correlation analysis and multiple linear regression analysis were used to explore the correlations between dietary quality during pregnancy and fetal immune function. The mean score of total DQI-P score of the study subjects was 55.8±10.0, and the mean score of overall food diversity and protein food source diversity was as high as 12.0±2.4 and 4.8±0.7. The mean score of nutrient energy ratio and fatty acid energy ratio was only 0.3±1.0 and 0.4±1.0, indicating that the population had good dietary diversity during pregnancy, but the dietary adequacy, suitability and balance were poor. The total score of DBI-P score was-19.2±9.4. The positive end score was 4.6±2.9, only 7.2% of the subjects had a high degree of dietary intake during pregnancy. The negative end score was 23.9±7.9, indicating the status of moderate dietary intake. Dietary quality was 28.5±7.1. Only 0.6% of the study population had a balanced dietary situation, and more than 67.9% of pregnant women had high intake imbalance. The mean total score of aMED score was 4.9±1.3, and the proportion of the food intake of beans and nuts was less than the median population was 62.5% and 79.1%, respectively, indicating that the food intake of beans and nuts was insufficient in this population. After adjusting for confounding factors such as maternal age, parity, parity, prepregnancy BMI, weight gain during pregnancy, and mode of delivery, multiple linear regression analysis showed DQI-P during pregnancy and negatively with IL-6(β=0.143, β=-0.155, P<0.05). DBI-P was negatively associated with IL-6(β=-0.177, P<0.01) and aMED and IFN-γ(β=-0.161, P<0.01). The dietary quality of women in late pregnancy in Guangzhou is low, the dietary structure is unbalanced. Higher dietary quality during pregnancy can promote the development of fetal immune system and improve fetal immune function.

Gut-lung axis and asthma: A historical review on mechanism and future perspective.

Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut-lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic. BODY: This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut-lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed. The gut-lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.

Disruption of post-thymic tolerance in skin-reactive TCR transgenic mice through the interaction of lymphopenia and intestinal microbiota.

Autoimmune diseases often arise from conditions where the immune system is compromised. While lymphopenia-induced proliferation (LIP) is crucial for immune system development and maturation, it is also caused by environmental insults, such as infection, and becomes a risk factor for autoimmunity in adults. We used Dsg3H1 TCR transgenic mice, whose T cells are designed to recognize desmogrein-3, a skin antigen, to explore the impact of lymphopenia on post-thymic tolerance. Dsg3H1 mice are known to delete the most highly autoreactive T cells in the thymus, and develop only subtle immune-mediated pathology in the steady state. However, we found that transient lymphopenia induced by total body irradiation (TBI) or cyclophosphamide (CY) results in massive dermatitis in Dsg3H1 mice. The symptoms included expansion and development of self-reactive T cells, their differentiation into CD44high IL-17-producing helper T cells, and severe neutrophilic inflammation. Repopulation of FOXP3+ T regulatory cells after lymphopenia normally occurred, suggesting escape of skin-reactive conventional T cells from control by regulatory T cells. Furthermore, we found that a depletion of the intestinal microbiota by antibiotics prevents CY-induced dermatitis, indicating roles of the commensal intestinal microbiota in LIP and Th17 development in vivo. The current data suggested that post-thymic tolerance of Dsg3H1 mice is established on a fragile balance in the lymphoreplete immune environment and broken by the interplay between lymphopenia and intestinal microbiota. The dynamic phenotypes observed in Dsg3H1 mice prompt a re-evaluation of opportunistic lymphopenia together with the microbiota as pivotal environmental factors, impacting individuals with genetic predispositions for autoimmune diseases.

The Effect of Maternal Hormones on the Avian Offspring: A Review

Maternal hormones have a significant impact on the development of avian embryos, controlling vital physiological functions such as immune system development, metabolism control, and productive traits. This review will examine the different types of maternal hormones, synthesis, regulation, and effects on avian physiology and productivity, as well as the implications for embryonic development. Additionally, it appears that how they might affect hatchability and chick quality. Studies have shown that maternal hormones transfer to eggs and subsequently affect the offspring's development, greatly influencing the behavior and phenotype of avian offspring overall. Understanding these mechanisms can help improve our knowledge of developmental biology, parental investment, and evolutionary processes that influence avian traits. Different species of birds may experience different effects when exposed to maternal hormones. For example injecting testosterone into bird eggs can increase the rate at which certain species hatch, such as quail, other species may see a decrease in hatchling weight. This emphasizes the complexity of hormonal influences on bird development and the necessity of more research. In particular, it is still unclear how yolk steroids affect birds' immune systems; early research indicates that they may chickens' ability to produce antibodies. Undertaking further research is necessary to completely understand the implications of avian immunity to fill in these gaps in knowledge across species and developmental stages.

Human gut microbiome, diet, and mental disorders.

Diet is one of the most important external factor shaping the composition and metabolic activities of the gut microbiome. The gut microbiome plays a crucial role in host health, including immune system development, nutrients metabolism, and the synthesis of bioactive molecules. In addition, the gut microbiome has been described as critical for the development of several mental disorders. Nutritional psychiatry is an emerging field of research that may provide a link between diet, microbial function, and brain health. In this study, we have reviewed the influence of different diet types, such as Western, Mediterranean, vegetarian, and ketogenic, on the gut microbiota composition and function, and their implication in various neuropsychiatric and psychological disorders.

Abstract 2163: Socioeconomic status associates with epigenetic modulation of TET2: An emerging pathway in cardio-oncology

Abstract Introduction: Adverse social determinants of health (SDOH) are known to accelerate poor outcomes in cardiovascular disease (CVD) and cancer. Clonal Hematopoiesis (CH) is a mechanism implicated in these disease states, partially driven by epigenetic regulatory genes, including TET2. Yet, there is not much known about how epigenetic modulations of TET2 itself may relate to the immune system and subsequent disease development. Hypothesis: We hypothesize that socioeconomic status (SES), as a SDOH marker, relates to epigenetic modulation of TET2. Methods: 60 African American adults (93.3% female, mean age 61) with CVD risk, living in the Washington, D.C. area self-reported their SES as household income. Immune system activity was assessed via splenic activity (SpleenA) by 18FDG PET/CT. Serum cytokine levels were measured by ELISA and DNA methylation analysis evaluated the epigenetic modulations of TET2. Multivariable regression analysis adjusted for ASCVD 10-year risk score and BMI was used to examine associations. Results: Out of 33 TET2 methylation sites, we found 3 sites that were significantly related to SES. Notably, only Tet2cg09666717 (SES β=0.310, p=0.038) was also associated with SpleenA (β=-0.453, p=0.036) and several cytokines: IL-17A, IL-1β and TNFα along with trending to significance with IFN-γ (Table). Conclusion: Thus, we found that SES associates with hypomethylation of Tet2cg09666717, which further related to SpleenA and inflammatory markers. Our findings are hypothesis generating and suggest that lower SES may relate to inflammation and immune system dysregulation by the way of epigenetic modulation of TET2. These results should be examined in larger, functional studies with diverse population-based cohorts to determine the potential relationships of both SDOH and epigenetic markers in CH and cardio-oncology outcomes. Associations between TET2 methylation sites, SpleenA, SES and Cytokines in DCCNHA cohort, 2014-17 Tet2cg09666717 Tet2cg05094833 Tet2cg10594473 SES 0.310 (0.038) -0.405 (0.006) -0.283 (0.060) Splenic Activity -0.453 (0.036) 0.004 (0.985) 0.097 (0.654) IL-6 -0.078 (0.558) -0.211 (0.108) -0.222 (0.084) IL-8 -0.199 (0.153) 0.024 (0.865) -0.004 (0.979) IL-17A -0.373 (0.010) 0.134 (0.370) -0.434 (0.017) IL-1β -0.382 (0.003) 0.042 (0.757) -0.143 (0.275) TNFα -0.456 (0.000) -0.157 (0.244) 0.005 (0.969) IFN-γ -0.258 (0.062) -0.037 (0.790) 0.022 (0.876) Data are presented as standardized β coefficient (p-value). All data are adjusted for 10-year predicted ASCVD risk and BMI; ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; IL-6 = interleukin 6; IL-8 = interleukin 8; IL-17A = interleukin 17A; IL-1β = interleukin 1 beta; TNFα = tumor necrosis factor; IFN-γ = interferon gamma Citation Format: Sonal Sharda, Yvonne Baumer, Alina P. Pang, Abhinav Saurabh, Billy S. Collins, Valerie M. Mitchell, Michael J. Corley, Tiffany M. Powell-Wiley. Socioeconomic status associates with epigenetic modulation of TET2: An emerging pathway in cardio-oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2163.

Elucidating the role of ZRF1 in monocyte-to-macrophage differentiation, cell proliferation and cell cycle in THP-1 cells

Abstract Objectives ZRF1 (Zuotin-related factor 1) is a versatile protein engaged in protein folding, gene regulation, cellular differentiation, DNA damage response, and immune system and cancer development regulation. This study investigates the role of ZRF1 in monocyte-to-macrophage transformation, and its effects on cell proliferation and the cell cycle. Methods We generated ZRF1-depleted THP-1 cells and induced macrophage differentiation using phorbol 12-myristate 13-acetate (PMA). Differentiation was assessed via microscopy and flow cytometry, while cell proliferation was quantified with the [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] (MTS) assay, and the cell cycle was analyzed through flow cytometry using propidium iodide staining. Results ZRF1-depleted THP-1 cells exhibited notable morphological changes. Flow cytometry post-PMA treatment indicated these cells were smaller and less granular than controls. Proliferation rates of ZRF1-depleted monocytes and macrophages were significantly higher than controls, particularly over longer durations. Cell cycle analysis showed ZRF1 depletion notably affected the G0-G1 phase, highlighting its significant role in macrophage differentiation. Conclusions The findings provide important insights into ZRF1’s role in monocyte-to-macrophage differentiation and its impact on cell proliferation and the cell cycle. This research not only supports existing knowledge about ZRF1 but also enhances our understanding of its multifaceted roles in cellular processes.

Early life imprinting of intestinal immune tolerance and tissue homeostasis.

Besides its canonical role in protecting the host from pathogens, the immune system plays an arguably equally important role in maintaining tissue homeostasis. Within barrier tissues that interface with the external microenvironment, induction of immune tolerance to innocuous antigens, such as commensal, dietary, and environmental antigens, is key to establishing immune homeostasis. The early postnatal period represents a critical window of opportunity in which parallel development of the tissue, immune cells, and microbiota allows for reciprocal regulation that shapes the long-term immunological tone of the tissue and subsequent risk of immune-mediated diseases. During early infancy, the immune system appears to sacrifice pro-inflammatory functions, prioritizing the establishment of tissue tolerance. In this review, we discuss mechanisms underlying early life windows for intestinal tolerance with a focus on newly identified RORγt+ antigen-presenting cells-Thetis cells-and highlight the role of the intestinal microenvironment in shaping intestinal immune system development and tolerance.

Microbiome: Mammalian milk microbiomes: sources of diversity, potential functions, and future research directions.

Milk is an ancient, fundamental mammalian adaptation that provides nutrition and biochemical communication to offspring. Microbiomes have been detected in milk of all species studied to date. In this review, we discuss: (a) routes by which microbes may enter milk; (b) evidence for proposed milk microbiome adaptive functions; (c) variation in milk microbiomes across mammals; and (d) future research directions, including suggestions for how to address outstanding questions on the viability and functionality of milk microbiomes. Milk microbes may be sourced from the maternal gastrointestinal tract, oral, skin, and mammary gland microbiomes and from neonatal oral and skin microbiomes. Given the variety of microbial sources, stochastic processes strongly influence milk microbiome assembly, but milk microbiomes appear to be influenced by maternal evolutionary history, diet, environment, and milk nutrients. Milk microbes have been proposed to colonize the neonatal intestinal tract and produce gene and metabolic products that influence physiology, metabolism, and immune system development. Limited epidemiological data indicate that early-life exposure to milk microbes can result in positive, long-term health outcomes. Milk microbiomes can be modified by dietary changes including providing the mother with probiotics and prebiotics. Milk replacers (i.e. infant formula) may benefit from supplementation with probiotics and prebiotics, but data are lacking on probiotics' usefulness, and supplementation should be evidence based. Overall, milk microbiome literature outside of human and model systems is scarce. We highlight the need for mechanistic studies in model species paired with comparative studies across mammals to further our understanding of mammalian milk microbiome evolution. A broader study of milk microbiomes has the potential to inform animal care with relevance to ex situ endangered species. Milk is an ancient adaptation that supports the growth and development of mammalian neonates and infants. Beyond its fundamental nutritional function, milk influences all aspects of neonatal development, especially immune function. All kinds of milks so far studied have contained a milk microbiome. In this review, we focus on what is known about the collection of bacterial members found in milk microbiomes. Milk microbiomes include members sourced from maternal and infant microbiomes and they appear to be influenced by maternal evolutionary history, diet, milk nutrients, and environment, as well as by random chance. Once a neonate begins nursing, microbes from milk colonize their gut and produce byproducts that influence their physiology, metabolism, and immune development. Empirical data on milk microbiomes outside of humans and model systems are sparse. Greater study of milk microbiomes across mammals will expand our understanding of mammalian evolution and improve the health of animals under human care.

Gut bacteria-derived serotonin promotes immune tolerance in early life.

The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell-mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.

Transcriptome analysis of the Nile tilapia (Oreochromis niloticus) reveals altered expression of immune genes by cadmium

Nile tilapia (Oreochromis niloticus) is a worldwide farmed fish and has been widely used for the study on comparative immunology in teleosts. It is well known that cadmium (Cd) can cause a variety of adverse effects in fish. However, data on the effects of Cd in fish liver and the defensive mechanisms of these effects using transcriptome approach are relatively scarce to date. In this study, by using an RNA sequencing approach, the gene expression profiling was performed in livers of tilapia exposed to 0 (control), 50, 100, and 200 μg/L of Cd for 2 months. The results showed that exposure to 50 μg/L Cd altered the expressions of 911 genes, while exposure to 100 and 200 μg/L Cd resulted in 4318 and 3737 differentially expressed genes compared to the control. Weighted correlation network analysis (WGCNA) and gene ontology (GO) analysis identified a 14-gene network linked to the immune system development. Further, in a fuzzy analysis, the GO term immune system development was enriched in cluster 3, and gene expression decreased with increasing Cd levels in a concentration-dependent manner. The qPCR and RNA-seq results identified 4 genes, i.e., dnmt3bb.1, sf3b1, SMARCAL1, and zap70, as convenient potential biological indicators for detecting waterborne Cd. The present results help systematically understand the effects of Cd on the hepatic transcriptome in tilapia.

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.

Stochasticity in genetics and gene regulation.

Development from fertilized egg to functioning multi-cellular organism requires precision. There is no precision, and often no survival, without plasticity. Plasticity is conferred partly by stochastic variation, present inherently in all biological systems. Gene expression levels fluctuate ubiquitously through transcription, alternative splicing, translation and turnover. Small differences in gene expression are exploited to trigger early differentiation, conferring distinct function on selected individual cells and setting in motion regulatory interactions. Non-selected cells then acquire new functions along the spatio-temporal developmental trajectory. The differentiation process has many stochastic components. Meiotic segregation, mitochondrial partitioning, X-inactivation and the dynamic DNA binding of transcription factor assemblies-all exhibit randomness. Non-random X-inactivation generally signals deleterious X-linked mutations. Correct neural wiring, such as retina to brain, arises through repeated confirmatory activity of connections made randomly. In immune system development, both B-cell antibody generation and the emergence of balanced T-cell categories begin through stochastic trial and error followed by functional selection. Aberrant selection processes lead to immune dysfunction. DNA sequence variants also arise through stochastic events: some involving environmental fluctuation (radiation or presence of pollutants), or genetic repair system malfunction. The phenotypic outcome of mutations is also fluid. Mutations may be advantageous in some circumstances, deleterious in others. This article is part of a discussion meeting issue 'Causes and consequences of stochastic processes in development and disease'.

Current insights into microbiome-based therapy. Review

Current insights into microbiome-based therapy. Review

Immunophenotypes of Newborns From SARS-CoV-2-infected Mothers.

Little is known about the neonatal immunologic response to a maternal SARS-CoV-2 infection present during childbirth. Here we analyze a cohort of 75 neonates from SARS-CoV-2-infected mothers. The SARS-CoV-2 infection status was laboratory assessed by real-time reverse transcription polymerase chain reaction on nasopharyngeal swabs (NPS) in both mothers during childbirth and neonates within 24 hours of life. Immunophenotypes of peripheral blood mononucleated cells and SARS-CoV-2 antispike IgA, IgM and IgG of the newborns were recorded. Ten (13.3%) of 75 neonates had positive NPS for SARS-CoV-2; 17 of 75 (23%) were SARS-CoV-2-IgG seropositive, of which one with positive NPS. All the newborns resulted seronegative for SARS-CoV-2 IgA and IgM and were asymptomatic. Our cohort of newborns was divided into groups according to IgG seropositivity (IgG+/-) and NPS results (NPS+/-). The count and proportion of lymphocyte subsets (evaluated measuring CD3, CD4, CD8 and CD19 markers) and of natural killer cells (evaluated by measuring the CD3-/CD16+/CD56+ subset) were all in the normal range, with no statistical differences among groups. We found a significant expansion of the T cell (CD3+) subset in the IgG+ group interpreted as the result of immune effects triggered by trained immunity in these newborns, but a decrease in CD4+ T cells for NPS+ neonates. It is therefore difficult to conclude that the decrease in CD4 can certainly be caused by an infection. A maternal SARS-CoV-2 infection resulted in an expansive effect of CD3+ T cells in IgG+ newborns; nonetheless, it seems not to affect structural and functional development of the newborn immune system.

Mammary epithelium permeability during established lactation: associations with cytokine levels in human milk.

The cytokine profile of human milk may be a key indicator of mammary gland health and has been linked to infant nutrition, growth, and immune system development. The current study examines the extent to which mammary epithelium permeability (MEP) is associated with cytokine profiles during established lactation within a sample of US mothers. Participants were drawn from a previous study of human milk cytokines. The present analysis includes 162 participants (98 Black, 64 White) with infants ranging from 1 to 18 months of age. Levels of cytokines were determined previously. Here we measure milk sodium (Na) and potassium (K) levels with ion-selective probes. Two approaches were used to define elevated MEP: Na levels ≥10 mmol/L and Na/K ratios greater than 0.6. Associations between maternal-infant characteristics, elevated MEP, and twelve analytes (IL-6, IL-8, TNFα, IL-1β, FASL, VEGFD, FLT1, bFGF, PLGF, EGF, leptin, adiponectin) were examined using bivariate associations, principal components analysis, and multivariable logistic regression models. Elevated MEP was observed in 12 and 15% of milk samples as defined by Na and Na/K cutoffs, respectively. The odds of experiencing elevated MEP (defined by Na ≥ 10 mmol/L) were higher among Black participants and declined with older infant age. All cytokines, except leptin, were positively correlated with either Na or the Na/K ratio. A pro-inflammatory factor (IL-6, IL-8, TNFα, IL-1β, EGF) and a tissue remodeling factor (FASL, VEGFD, FLT1, bFGF, PLGF, adiponectin) each contributed uniquely to raising the odds of elevated MEP as defined by either Na or the Na/K ratio. This exploratory analysis of MEP and cytokine levels during established lactation indicates that elevated MEP may be more common in US populations than previously appreciated and that individuals identifying as Black may have increased odds of experiencing elevated MEP based on current definitions. Research aimed at understanding the role of MEP in mammary gland health or infant growth and development should be prioritized.

Microbiota in the first 1000 days: Effect on health and diseases

The first 1000 days before or after birth are pivotal for the establishment of early-life microbial communities and the development of the immune system. During this critical period, alterations in the microbial composition within the gastrointestinal tract significantly impact various host developmental pathways, including those related to immunity, endocrine function, and metabolism.The term "first 1000 days" encompasses the period from conception to 2 years of age. Disturbances to the microbiota within this timeframe can have enduring consequences for an infant's health, contributing to the onset of inflammatory and autoimmune disorders, neurological issues, and obesity.Several maternal factors, including gestational age, delivery mode, maternal vaginal microbiota, maternal health, diet, and exposure to antibiotics during pregnancy and lactation, exert a profound influence on the infant's gut microbiota. Environmental factors such as delivery mode, gestational age, and breastfeeding also play a crucial role. Ongoing research aims to explore early-life interventions that can modify both gut microbiota and immune system development. Ensuring a healthy intestinal microbial community during pregnancy and infancy is indispensable for securing favorable long-term health outcomes for the infant.The microbiome undergoes significant transformations during this developmental period, primarily influenced by changes in diet and environmental factors. Epigenetic modifications emerge as crucial mechanisms through which environmental factors impact early cellular differentiation, giving rise to new phenotypic traits within the neonatal period, without altering the DNA sequence.Implementing measures to minimize dysbiosis, a condition linked to the severity of Food Allergies (FAs), is essential. Breastfeeding emerges as a fundamental practice in reducing intestinal inflammation, with Human Milk Oligosaccharides (HMOs) playing a prebiotic role in this context. Future strategies may include interventions to positively modulate the composition of the gut microbiota, especially in children with a family history of atopy.

Immunological Challenges in Infants Living with HIV: A Review

This paper explores the intricate immunological challenges encountered by infants living with Human Immunodeficiency Virus (HIV). The vulnerability of the developing immune system in early life, coupled with the unique characteristics of HIV, presents a complex scenario that impacts the health and well-being of these infants. Key areas of focus include the disruption of immune system development, viral persistence mechanisms, consequences of chronic immune activation, and the increased susceptibility to opportunistic infections. The paper also discusses current therapeutic interventions, emphasizing the significance of early antiretroviral therapy (ART) initiation and emerging strategies aimed at improving immunological outcomes. Insights into the maternal-fetal interface and preventive measures are explored, providing a holistic perspective on addressing the challenges faced by infants born with HIV. This comprehensive analysis aims to contribute to a deeper understanding of the immunological landscape in this vulnerable population and guide future research and interventions for enhanced patient care.