Innate Immune Function Research Articles

Seasonal Immune Rhythms of head kidney and spleen cells in the freshwater Teleost, Channa punctatus

Annual rhythms in immune function are the reflection of a crucial physiological strategy to deal with environmental stressors. The fish are pivotal animal models to study the annual rhythm and to understand the evolution of the vertebrate biological system. The current research was planned to assess the annual changes in the innate immune functions of immune cells in a teleost, Channa punctatus. Head kidney and splenic macrophage phagocytosis, superoxide generation, and nitrite release were evaluated to assess innate immunity. Cell-mediated immunity was measured through head kidney and splenic lymphocyte proliferation in presence of mitogens. The superoxide anion generation by the cells of head kidney and spleen was maximum in October. A bimodal pattern in nitrite production was observed with the first peak in November and the second in March. Cosinor analysis revealed a statistically significant annual rhythm in nitrite production. Similarly, phagocytosis and lymphocyte proliferation also showed statistically significant annual rhythms. It was concluded that animals maintain an optimum immune response in seasonally changing environments. Elevated immunity during certain times of the year might assist animals deal with seasonal environmental stressors. Further research may be focused upon measuring survival rate and reproductive success after season induced elevated immunity.

Targeting the stimulator of interferon genes (STING) in breast cancer.

Breast cancer has a high occurrence rate globally and its treatment has demonstrated clinical efficacy with the use of systemic chemotherapy and immune checkpoint blockade. Insufficient cytotoxic T lymphocyte infiltration and the accumulation of immunosuppressive cells within tumours are the primary factors responsible for the inadequate clinical effectiveness of breast cancer treatment. The stimulator of interferon genes (STING) represents a pivotal protein in the innate immune response. Upon activation, STING triggers the activation and enhancement of innate and adaptive immune functions, resulting in therapeutic benefits for malignant tumours. The STING signalling pathway in breast cancer is influenced by various factors such as deoxyribonucleic acid damage response, tumour immune microenvironment, and mitochondrial function. The use of STING agonists is gaining momentum in breast cancer research. This review provides a comprehensive overview of the cyclic guanosine monophosphate-adenosine monophosphate synthase-STING pathway, its agonists, and the latest findings related to their application in breast cancer.

Astragalus regulates the intestinal immune response during sepsis by mediating ILC3 proliferation through RORγt

BackgroundSepsis is a common complication of many diseases and is associated with high morbidity and mortality rates. Astragalus can improve humoral and innate immunity, inhibit inflammatory responses, and protect immune cells and organs from damage. However, to the best of our knowledge there are no reports on whether astragalus can regulate intestinal innate immune function during sepsis. MethodsIn this study, a rat cecal ligation and puncture model of sepsis was used to investigate the effects of astragalus treatment, following which the apoptosis rate of lymphocytes from Peyer’s patches (PP) was determined. Type 3 innate lymphoid cells (ILC3) were cultured in vitro to further evaluate the effects and mechanisms of astragalus. ResultsThe apoptosis level of lymphocytes from PP in rats with sepsis was significantly increased, and the number of ILC3 was significantly reduced, compared with the sham operation group, which aggravated intestinal injury and ultimately led to the death of rats. Astragalus treatment significantly inhibited the apoptosis of lymphocytes from PP, increased the number of ILC3, and improved the intestinal inflammatory environment compared to the sepsis group. RT-PCR revealed that astragalus and the retinoic acid-related orphan receptor γt (RORγt) agonist LYC-55716 both promote the expression of interleukin (IL)-17A, IL-17F, IL-22, interferon-γ, and granulocyte-macrophage colony-stimulating factor mRNA. Mechanistically, astragalus promotes the proliferation of ILC3 through RORγt, thereby reducing intestinal inflammatory damage. ConclusionAstragalus, via RORγt, promotes the generation of ILC3, improves the inflammatory environment in rats with sepsis.

Innate immune activation and aberrant function in the R6/2 mouse model and Huntington's disease iPSC-derived microglia.

Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disease caused by CAG repeats in exon 1 of the HTT gene. A hallmark of HD along with other psychiatric and neurodegenerative diseases is alteration in the neuronal circuitry and synaptic loss. Microglia and peripheral innate immune activation have been reported in pre-symptomatic HD patients; however, what "activation" signifies for microglial and immune function in HD and how it impacts synaptic health remains unclear. In this study we sought to fill these gaps by capturing immune phenotypes and functional activation states of microglia and peripheral immunity in the R6/2 model of HD at pre-symptomatic, symptomatic and end stages of disease. These included characterizations of microglial phenotypes at single cell resolution, morphology, aberrant functions such as surveillance and phagocytosis and their impact on synaptic loss in vitro and ex vivo in R6/2 mouse brain tissue slices. To further understand how relevant the observed aberrant microglial behaviors are to human disease, transcriptomic analysis was performed using HD patient nuclear sequencing data and functional assessments were conducted using induced pluripotent stem cell (iPSC)-derived microglia. Our results show temporal changes in brain infiltration of peripheral lymphoid and myeloid cells, increases in microglial activation markers and phagocytic functions at the pre-symptomatic stages of disease. Increases in microglial surveillance and synaptic uptake parallel significant reduction of spine density in R6/2 mice. These findings were mirrored by an upregulation of gene signatures in the endocytic and migratory pathways in disease-associated microglial subsets in human HD brains, as well as increased phagocytic and migratory functions of iPSC-derived HD microglia. These results collectively suggest that targeting key and specific microglial functions related to synaptic surveillance and pruning may be therapeutically beneficial in attenuating cognitive decline and psychiatric aspects of HD.

Differential Activities of the Botanical Extract PBI-05204 and Oleandrin on Innate Immune Functions under Viral Challenge Versus Inflammatory Culture Conditions.

The Nerium oleander extract PBI 05204 (PBI) and its cardiac glycoside constituent oleandrin have direct anti-viral properties. Their effect on the immune system, however, is largely unknown. We used an in vitro model of human peripheral blood mononuclear cells to document effects under three different culture conditions: normal, challenged with the viral mimetic polyinosinic:polycytidylic acid Poly I:C, and inflamed by lipopolysaccharide (LPS). Cells were evaluated for immune activation marks CD69, CD25, and CD107a, and culture supernatants were tested for cytokines. Both PBI and oleandrin directly activated Natural Killer (NK) cells and monocytes and triggered increased production of cytokines. Under viral mimetic challenge, PBI and oleandrin enhanced the Poly I:C-mediated immune activation of monocytes and NK cells and enhanced production of IFN-γ. Under inflammatory conditions, many cytokines were controlled at similar levels as in cultures treated with PBI and oleandrin without inflammation. PBI triggered higher levels of some cytokines than oleandrin. Both products increased T cell cytotoxic attack on malignant target cells, strongest by PBI. The results show that PBI and oleandrin directly activate innate immune cells, enhance anti-viral immune responses through NK cell activation and IFN-γ levels, and modulate immune responses under inflamed conditions. The potential clinical impact of these activities is discussed.

The effect of dietary antioxidant vitamins on malondialdehyde, white blood cells, and platelets

Introduction: Vitamins have a main role in controlling metabolism in the body and the immune system. Vitamins A, C, and E are known as antioxidant nutrients and vitamin D is essential for innate and adaptive immune function. This study is aimed to analyze the effect of vitamin intake regularly on malondialdehyde (MDA) levels, white blood cell (WBCs) and platelet counts, and differences count of leukocyte Method: The study used 6 groups including the control group without intervention and the intervention group intake of one tablet of vitamin a day for 7 days which were divided into groups of vitamin A 2000 IU, vitamin C 1000 mg, vitamin D 400 IU, vitamin E 100 IU and multivitamins C 1000 mg and D 400 IU Results: Based on the study was explained that vitamins C, D, and E and multivitamins C and D were able to reduce MDA levels and leukocyte counts descriptively but not significantly. The differential leukocyte count has various levels depending on the type of vitamin. Conclusion: Therefore, the consumption of vitamins A, C, D, and E and multivitamins C and D had no significant effect on MDA levels, WBCs count, platelets count, and differential count of leukocyte.

Melatonin Alters Innate Immune Function in Infants with Neonatal Encephalopathy

Introduction: Melatonin has been suggested an adjunctive therapy in neonatal encephalopathy (NE). Melatonin reduces oxidative stress and neutrophil activation; however, the immunological effects in NE have not been studied. Methods: Infants with NE and neonatal controls were prospectively recruited. Whole blood was sampled in the first week of life. Following endotoxin and or melatonin treatment, diurnal variation was measured by RT PCR for circadian rhythm genes (brain and Muscle Arnt-Like protein [BMAL1], circadian locomotor output cycles kaput [CLOCK], Nuclear Receptor Subfamily 1 Group D Member 2 [REV Erβ], and cryptochrome circadian clock [CRY]). Neutrophil and monocyte cell surface markers of activation CD11b, reactive oxygen intermediates (ROIs), and Toll-like receptor (TLR)-4 were also examined by flow cytometry in matching samples. Results: Serum and RNA samples from forty infants were included (controls n = 20; NE n = 20) over the first week of life. Melatonin reduced neutrophil CD11b and TLR-4 expression in response to LPS in infants with NE compared to controls. There were no differences in ROIs. BMAL1 and CLOCK baseline gene expression levels were similar. BMAL1 was significantly decreased with LPS stimulation in NE. There was no significant diurnal variation in melatonin, neutrophil, and monocyte function or circadian genes. Conclusions: Melatonin alters immune function ex vivo in infants with NE. Infants with NE have altered immune circadian responses following LPS stimulation, which have potential for modulation.

DIPG-04. TUMOR CELL-INTRINSIC TIM-3 PROMOTES DIFFUSE INTRINSIC PONTINE GLIOMA TUMORIGENESIS

Abstract Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor and the leading cause of pediatric death caused by cancer. Despite great strides in the understanding of this disease, the median overall survival is still dismal. TIM-3 is emerging as an alternative to the classic immune checkpoints CTLA-4 and PD-1, and its expression regulates by various mechanisms the function of innate and adaptative immunity. In our work, we demonstrated that TIM-3 is expressed in murine and human DIPG tumor cell lines in vitro and in vivo. TIM-3 knockout using CRISPR/Cas9 was lethal in all human DIPG cell lines evaluated. However, a doxycycline-inducible shRNA-TIM-3 significantly reduced the proliferation of DIPG human cell lines (100% control vs. 25% shRNA TIM-3). Additionally, TIM-3KO murine cell lines displayed a significant decrease in clonogenicity, proliferation, and migration in vitro compared with parental DIPG murine cell lines. Interestingly, loss of TIM-3 expression did not result in cell death, as shown by the evaluation of apoptosis. In vivo evaluation of TIM-3KO cell lines tumorigenicity demonstrated that mice bearing TIM3-KO cells had an overall median survival (35 days) significantly higher than the ones bearing the control guide cells (16 days). RNAseq data indicated that TIM-3 plays a critical role in DIPG murine cells tumorigenesis and survival through the MAPK signaling pathway. Finally, single-cell sequencing and immunochemistry of human tumor samples uncovered TIM-3 expression in patients. TIM-3 expression in DIPG tumor cells correlated with genes positively involved in regulating ion transport, IL-6 production, and response to IFN-γ pathways. We also observed enrichment in genes regulating MAPK and ERK1/ERK2 cascades in these patients. Collectively, these data suggest that TIM-3 expression might have a role in the survival and tumorigenesis of DIPG cells.

IMMU-14. WAKING THE SLEEPING GIANT: TLR7/8 AGONIST TREATMENT STIMULATES TUMOR-ASSOCIATED MYELOID CELLS FOR MEDULLOBLASTOMA IMMUNOTHERAPY

Abstract Medulloblastomas contain large myeloid populations and we have identified a novel therapy that effectively recruits these non-tumor cells for anti-cancer effect. Medulloblastoma myeloid cells have bivalent functions, supporting tumor growth through IGF1 secretion and immunosuppression, or inhibiting tumor growth through diverse mechanisms including phagocytosis. We investigated a nanoparticle formulation of the TLR7/8 agonist Resiquimod (POx-Resiquimod), administered to Gfap-Cre/SmoM2 (G-Smo) mice that are engineered to develop SHH medulloblastomas, using animal survival time studies, flow cytometry and single-cell trancriptomics (scRNA-seq). POx-Resiquimod treatment increased the survival of G-Smo mice as a single agent and sensitized the typically radiation-resistant G-Smo tumors to radiation therapy. Mechanistically, POx-resiquimod increased the proportions of myeloid cells in medulloblastoma, while blocking IGF1 secretion and re-polarizing the myeloid population from anti-inflammatory to pro-inflammatory. POx-resiquimod induced phagocytosis-related genes, including CD72 and the scavenger receptor MARCO. Functional studies confirmed that POx-resiquidmod increased tumor cell phagocytosis, linking molecular changes to changes in myeloid cell behavior. Our data show that the innate immune function of myeloid cells can be harnessed for medulloblastoma treatment and identify the nanoparticle-delivered TLR7/8 agonist POx-Resiquimod as a specific and effective new agent for medulloblastoma immunotherapy that can be combined with existing modalities.

Genesis of clinical and subclinical endometritis in dairy cows.

Up to half of dairy cows may develop one or more types of reproductive tract inflammatory disease within 5 weeks after calving. Clinical endometritis (CE) results from uterine bacterial dysbiosis with increased relative abundance of pathogenic bacteria associated with luminal epithelial damage. These bacteria cause endometrial stromal cell lysis, followed by massive polymorphonuclear neutrophil (PMN) migration, and pyogenesis. Clinical endometritis is defined as endometrial inflammation accompanied by purulent discharge. Purulent discharge is not always accompanied by uterine inflammation (being (rarely) vaginitis or (commonly) cervicitis), hence referred to as purulent vaginal discharge (PVD). Subclinical endometritis (SCE) is an asymptomatic uterine disease defined by a threshold of PMN on cytology that is associated with worse reproductive performance; it has not been linked with bacterial dysbiosis. Current evidence suggests that SCE is a result of metabolic and inflammatory dysfunction that impairs innate immune function and the ability of endometrial PMN to undergo apoptosis, necrosis, and ultimately achieve resolution of inflammation. Clinical endometritis and SCE are diagnosed between 3 and 5 weeks postpartum and commonly overlap, but they are considered distinct manifestations of reproductive tract inflammatory disease. This review addresses the genesis of CE and SCE in postpartum dairy cows considering metabolic stress, innate immune dysfunction, and shifts in the composition of the uterine microbiota.

34-kDa salivary protein enhances duck Tembusu virus infectivity in the salivary glands of Aedes albopictus by modulating the innate immune response

Duck Tembusu virus (DTMUV) is an important flavivirus that can be transmitted to poultry via Aedes albopictus bites. Furthermore, humans residing in the DTMUV epidemic area display activated antiviral immune responses to local DTMUV isolates during the pathogenic invasion, thereby raising the primary concern that this flavivirus may be transmitted to humans via mosquito bites. Therefore, we identified the gene AALF004421, which is a homolog of the 34-kDa salivary protein (34 kDa) of Ae. albopictus and studied the salivary protein-mediated enhancement of DTMUV infection in Ae. albopictus salivary glands. We observed that double-stranded RNA-mediated silencing of the 34 kDa in mosquito salivary glands demonstrated that the silenced 34 kDa impaired DTMUV infectivity, similar to inhibition through serine protease. This impairment occurred as a consequence of triggering the innate immune response function of a macroglobulin complement-related factor (MCR). 34-kDa in the salivary gland which had similar activity as a serine protease, results in the abrogation of antimicrobial peptides production and strong enhance DTMUV replication and transmission. Although the function of the 34 kDa in Ae. albopictus is currently unknown; in the present study, we showed that it may have a major role in DTMUV infection in mosquito salivary glands through the suppression of the antiviral immune response in the earliest stages of infection. This finding provides the first identification of a prominently expressed 34 kDa protein in Ae. albopictus saliva that could serve as a target for controlling DTMUV replication in mosquito vectors.

Black carbon nanoparticles activate the crosstalk mechanism between necroptosis and macrophage extracellular traps to change macrophages fate

PM2.5 still poses a threat to public health even at very low levels. Black carbon (BC) is a key component of PM2.5. Macrophage extracellular traps (METs) are a means by which macrophages capture and destroy invading pathogens. Necroptosis is an inflammatory programmed cell death. However, there is no research on the crosstalk mechanism between necroptosis and METs after BC exposure. In our study, fluorescence labeling, fluorescent probes, qPCR, and immunofluorescence were applied. Our research found that under normal physiological conditions, when macrophages receive external stimuli (in our experiment, phorbol 12-myristate 13-acetate (PMA)), they will form METs, thus exhibiting innate immune function. However, exposure to BC can cause necroptosis in macrophages accompanied by increased levels of ROS and cytosolic calcium ions as well as altered expression of inflammatory factors and chemokines that prevent the formation of METs, and weakening innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibits the formation of METs. Our experiment will enrich the understanding of the mechanism of macrophage injury caused by BC exposure, provide a new direction for studying harmful atmospheric particle toxicity, and propose new therapeutic insights for diseases caused by atmospheric particulate matter. This study is the first to explore the crosstalk mechanism between necroptosis and METs after BC exposure.

Immunological factor development of external genital endometriosis

External genital endometriosis (EGE) is one of the common gynecological diseases of women of reproductive age with a relapsing, progressive course that worsens the quality of life of patients due to pain, emotional imbalance, fear of relapse and possible surgical intervention. Currently, endometriosis is recognized as one of the most common diseases associated with infertility. Thus, among fertile women with preserved childbearing function, the disease is generally diagnosed in approximately 6-7%, while among patients suffering from infertility, its frequency can reach 20-48%.However, the causes that determine reproductive dysfunction in patients with EGE are not well understood. Much attention is currently paid to the role of immunity in the formation of endometriosis. Patients with EGE show changes in both local immunity factors and immunological components of circulating blood.Purpose of the study: the study of factors of innate and adaptive immunity in patients of reproductive age with external genital endometriosis (EGE).The study included 71 patients with various stages of external genital endometriosis, the control group included 24 patients without endometriosis. Determination of the population composition of peripheral blood lymphocytes, the level of monocytes expressing TLR, activation markers, was carried out by laser flow cytometry — Immunotex (France), Caltag (USA), FITC (fluorescein isothiocynate) — labeled CD3, CD4, CD8, CD16, CD19, HLA-DR, CD282, CD284 and PE (phycoerythrin) - labeled with CD25, CD69, CD95, CD107a, CD14.External genital endometriosis is characterized by: at stages I-II of the disease - a violation of the early stages of the innate immune response (an increase in the number of monocytes expressing TLR-4, a violation of the activation and differentiation processes of immunocompetent cells, which is reflected in a decrease in the expression of CD16, CD8, CD16+HLA-DR+, CD16+CD107a+, CD8+CD107a+, at III-IV stages of the disease, there is a decrease in the level of CD16 and activation markers CD69, HLA-DR, CD107a on their surface, which is combined with a decrease in the expression of CD8, CD16, HLADR and CD107a on their surface. CD95+ and CD8+CD95+ were found at various stages of EGE.The results obtained allow us to understand the features of the functioning of innate and adaptive immunity at various stages of external genital endometriosis, and the studied immunological parameters can be used as diagnostic criteria for the formation of various stages of EGE. These data can serve as a theoretical basis for further identification of markers of EGE progression, as well as the mechanisms underlying immune inflammation.

Gut Microbiota and Aging: Traditional Chinese Medicine and Modern Medicine.

The changing composition of gut microbiota, much like aging, accompanies people throughout their lives, and the inextricable relationship between both has recently attracted extensive attention as well. Modern medical research has revealed that a series of changes in gut microbiota are involved in the aging process of organisms, which may be because gut microbiota modulates aging-related changes related to innate immunity and cognitive function. At present, there is no definite and effective method to delay aging. However, Nobel laureate Tu Youyou's research on artemisinin has inspired researchers to study the importance of Traditional Chinese Medicine (TCM). TCM, as an ancient alternative medicine, has unique advantages in preventive health care and in treating diseases as it already has formed an independent understanding of the aging system. TCM practitioners believe that the mechanism of aging is mainly deficiency, and pathological states such as blood stasis, qi stagnation and phlegm coagulation can exacerbate the process of aging, which involves a series of organs, including the brain, kidney, heart, liver and spleen. Our current understanding of aging has led us to realise that TCM can indeed make some beneficial changes, such as the improvement of cognitive impairment. However, due to the multi-component and multi-target nature of TCM, the exploration of its mechanism of action has become extremely complex. While analysing the relationship between gut microbiota and aging, this review explores the similarities and differences in treatment methods and mechanisms between TCM and Modern Medicine, in order to explore a new approach that combines TCM and Modern Medicine to regulate gut microbiota, improve immunity and delay aging.

Transcriptomic Responses Underlying the High Virulence of Black Queen Cell Virus and Sacbrood Virus following a Change in Their Mode of Transmission in Honey Bees (Apis mellifera).

Over the last two decades, honey bees (Apis mellifera) have suffered high rates of colony losses that have been attributed to a variety of factors, chief among which are viral pathogens, such as deformed wing virus (DWV), whose virulence has increased because of vector-based transmission by the invasive, ectoparasitic varroa mite (Varroa destructor). A shift in the experimental mode of transmission of the black queen cell virus (BQCV) and sacbrood virus (SBV) from fecal/food-oral (direct horizontal) to vector-mediated (indirect horizontal) transmission also results in high virulence and viral titers in pupal and adult honey bees. Agricultural pesticides represent another factor that acts independently or in interaction with pathogens, and they are also thought to cause colony loss. Understanding the molecular mechanisms underlying the higher virulence following a vector-based mode of transmission provides deeper insight into honey bee colony losses, as does determining whether or not host-pathogen interactions are modulated by exposure to pesticides. Through an experimental design with controlled laboratory, we investigated the effects of the modes of transmission of BQCV and SBV (feeding vs. vector-mediated via injection) alone or in combination with chronic exposure to sublethal and field-realistic concentrations of flupyradifurone (FPF), a novel agricultural insecticide, on honey bee survival and transcription responses by using high-throughput RNA sequencing (RNA-seq) analysis. Co-exposure to viruses via feeding (VF) or injection (VI) and FPF insecticide had no statistically significant interactive effect on their survival compared to, respectively, VF or VI treatments alone. Transcriptomic analysis revealed a distinct difference in the gene expression profiles of bees inoculated with viruses via injection (VI) and exposed to FPF insecticide (VI+FPF). The number of differentially expressed genes (DEGs) at log2 (fold-change) > 2.0 in VI bees (136 genes) or/and VI+FPF insecticide (282 genes) was very high compared to that of VF bees (8 genes) or the VF+FPF insecticide treatment (15 genes). Of these DEGs, the expression in VI and VI+FPF bees of some immune-related genes, such as those for antimicrobial peptides, Ago2, and Dicer, was induced. In short, several genes encoding odorant binding proteins, chemosensory proteins, odor receptors, honey bee venom peptides, and vitellogenin were downregulated in VI and VI+FPF bees. Given the importance of these suppressed genes in honey bees' innate immunity, eicosanoid biosynthesis, and olfactory associative function, their inhibition because of the change in the mode of infection with BQCV and SBV to vector-mediated transmission (injection into haemocoel) could explain the high virulence observed in these viruses when they were experimentally injected into hosts. These changes may help explain why other viruses, such as DWV, represent such a threat to colony survival when transmitted by varroa mites.

New Insights into NF-κB Signaling in Innate Immunity: Focus on Immunometabolic Crosstalks.

The nuclear factor kappa B (NF-κB) is a family of transcription factors that, beyond their numberless functions in various cell processes, play a pivotal role in regulating immune cell activation. Two main pathways-canonical and non-canonical-are responsible for NF-κB activation and heterodimer translocation into the nucleus. A complex crosstalk between NF-κB signaling and metabolism is emerging in innate immunity. Metabolic enzymes and metabolites regulate NF-κB activity in many cases through post-translational modifications such as acetylation and phosphorylation. On the other hand, NF-κB affects immunometabolic pathways, including the citrate pathway, thereby building an intricate network. In this review, the emerging findings about NF-κB function in innate immunity and the interplay between NF-κB and immunometabolism have been discussed. These outcomes allow for a deeper comprehension of the molecular mechanisms underlying NF-κB function in innate immune cells. Moreover, the new insights are important in order to perceive NF-κB signaling as a potential therapeutic target for inflammatory/immune chronic diseases.

Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice

BackgroundPrevious studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis.ResultsThe study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5).ConclusionsBS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

Molecular Pathogenesis of Human Immunodeficiency Virus-Associated Disease of Oropharyngeal Mucosal Epithelium.

The oropharyngeal mucosal epithelia have a polarized organization, which is critical for maintaining a highly efficient barrier as well as innate immune functions. In human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) disease, the barrier and innate immune functions of the oral mucosa are impaired via a number of mechanisms. The goal of this review was to discuss the molecular mechanisms of HIV/AIDS-associated changes in the oropharyngeal mucosa and their role in promoting HIV transmission and disease pathogenesis, notably the development of opportunistic infections, including human cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. In addition, the significance of adult and newborn/infant oral mucosa in HIV resistance and transmission was analyzed. HIV/AIDS-associated changes in the oropharyngeal mucosal epithelium and their role in promoting human papillomavirus-positive and negative neoplastic malignancy are also discussed.

Heterorhabditis bacteriophora

Heterorhabditis bacteriophora is an insect parasite that first gained popularity as a means of agricultural pest control, but has also become a model for nematode parasitism. As an entomopathogenic nematode, H. bacteriophora serves as an obligate host for the Gram-negative bacteria Photorhabdus spp.; together, these symbiotic partners infect numerous insect species. When in contact with a potential host, the parasitic nematode enters through natural openings or pierces the cuticle of the insect to gain entry to the hemocoel, releasing the Photorhabdus spp. bacteria. Nematode virulence is influenced by the age of the infective juveniles. Using immunomodulatory strategies that interfere with innate immune signaling and function, the nematode–bacterial complex evades the insect host defense, which leads to increased virulence and accelerated insect death. H. bacteriophora is closely related to other Heterorhabditis spp. and is a burgeoning model for entomopathogenic nematode infections.

Elucidating the effects of acute and chronic exposure to 2,4-Dichlorophenoxyacetic acid on fathead minnow (Pimephales promelas) innate immunity

Aquatic herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D) formulations, are commonly used for invasive species management throughout the United States. Ecologically relevant concentrations of 2,4-D can impair essential behaviors, reduce survival, and act as an endocrine disruptor; however, there is limited knowledge of its effects on the health of non-target organisms. Here, we investigate the acute and chronic exposure impacts of 2,4-D on adult male and female fathead minnow (Pimephales promelas) innate immune function. We exposed both adult male and female fathead minnows to three different ecologically relevant concentrations of 2,4-D (0.00, 0.40, and 4.00 mg/L) and took blood samples at three acute time points (6, 24, and 96 h) and one chronic time point (30 days). We found that male fatheads had higher total white blood cell concentrations when exposed to 2,4-D at the acute time points. For the females, only proportions of specific cell types were altered when exposed to 2,4-D at the acute time points. However, we did not observe any significant impacts of chronic exposure to 2,4-D on any innate immune responses for either males or females. Overall, this study is the first step in answering an important question for game fisheries and management agencies while providing insight to future studies that investigate the impacts of herbicide exposure to freshwater fish health and immunity.