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Viruses May 2024Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral... (Review)
Review
Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral rotavirus vaccines in young children may be affected by significant immunological differences between individuals in early life and adults. Therefore, understanding the dynamics of early-life systemic and mucosal immune responses and the factors that affect them is essential to improve the current rotavirus vaccines and develop the next generation of mucosal vaccines. This review focuses on the advances in T-cell development during early life in mice and humans, discussing how immune homeostasis and response to pathogens is established in this period compared to adults. Finally, the review explores how this knowledge of early-life T-cell immunity could be utilized to enhance current and novel rotavirus vaccines.
Topics: Rotavirus Vaccines; Humans; Rotavirus Infections; Animals; Rotavirus; T-Lymphocytes; Administration, Oral; Immunity, Mucosal; Mice
PubMed: 38932111
DOI: 10.3390/v16060818 -
Pharmaceuticals (Basel, Switzerland) May 2024Microbicides, which are classified as topical antiseptic agents, are a revolutionary advancement in HIV prevention aimed to prevent the entry of infectious agents into... (Review)
Review
Microbicides, which are classified as topical antiseptic agents, are a revolutionary advancement in HIV prevention aimed to prevent the entry of infectious agents into the human body, thus stopping the sexual transmission of HIV and other sexually transmitted diseases. Microbicides represent the promise of a new age in preventive measures against one of the world's most pressing health challenges. In addition to their direct antiviral effects during HIV transmission, microbicides also influence vaginal mucosal immunity. This article reviews microbicides by presenting different drug classifications and highlighting significant representatives from each group. It also explains their mechanisms of action and presents information about vaginal mucosal immune responses, emphasizing the critical role they play in responding to HIV during sexual transmission. The article discusses the following groups of microbicides: surfactants or membrane disruptors, vaginal milieu protectors, anionic polymers, dendrimers, carbohydrate-binding proteins, HIV replication inhibitors (reverse transcriptase inhibitors), and multi-purpose prevention technologies, which combine protection against HIV, other sexually transmitted diseases, and contraception. For each chemical compound, the article provides a brief overview of relevant preclinical and clinical research, emphasizing their potential as microbicides. The article offers insights into the multifaceted impact of microbicides, which signify a pivotal step forward in the pursuit of effective and accessible pre-exposure prophylaxis (PrEP).
PubMed: 38931337
DOI: 10.3390/ph17060668 -
Microorganisms Jun 2024The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, () has relatively less...
The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, () has relatively less research on its antibacterial infection in vivo, and its protective effect and mechanism still need to be fully studied. In this study, we selected 23017, which can regulate the intestinal immunity of the host animal and resist pathogen infection, to evaluate its protective role and potential molecular mechanisms in the mouse model of C7731 infection. As expected, we confirmed that 23017 reduced the diarrhea rate and increased the daily weight gain and survival rate of the mouse model, and inhibited colonization in the jejunum and liver. It also reduced the level of oxidative damage and protected the integrity of intestinal tissue by increasing the activity of intestinal antioxidant enzymes (SOD, GSH-Px and T-AOC). From the perspective of intestinal mucosal barrier injury and repair, it was confirmed that 23017 could increase the expression levels of intestinal tight junction proteins (ZO-1 and OCLN). Our research results also show that 23017 inhibits the inflammatory response and promotes the occurrence of cellular immunity in the body by promoting the increase in IL-10 and inhibiting IL-13 in serum and intestinal tissue. Notably, 23017 increased total secretory immunoglobulin A (SIgA) levels in the intestine, which were closely associated with elevated levels of IL-5, IL-13, pIgR, j-chain, and IgAα-chain. In addition, 23017 increased the expression of antioxidant proteins Nrf2, NQO1, and HO-1 associated with Nrf2 signaling to inhibit intestinal oxidative damage. This mechanism may be responsible for its protective effect against -infected intestine. Our study provides new evidence and theoretical support for the analysis of the anti-bacterial infection effect and mechanism of , which will contribute to the development of and the treatment of pathogenic bacteria intestinal infection.
PubMed: 38930517
DOI: 10.3390/microorganisms12061135 -
Animals : An Open Access Journal From... Jun 2024This study assessed the impact of Magni-Phi Ultra (MPU) inclusion on intestinal integrity and immunity in broiler chickens challenged with coccidia during peak and...
This study assessed the impact of Magni-Phi Ultra (MPU) inclusion on intestinal integrity and immunity in broiler chickens challenged with coccidia during peak and recovery phases. A total of 128 male Ross 708 broiler chicks were randomly allotted to one of four treatment groups (four chicks/cage). Treatments included an uninfected control (UUC); a coccidial challenge (CC) infected control (IUC); a CC fed salinomycin at 66 ppm (SAL); and a CC fed Magni-Phi Ultra at 0.11 g/kg of diet (MPU). At 16 days post-hatch, all birds in the CC groups were orally gavaged with a 3× dose of a live coccidia vaccine. At 5 dpi, the birds fed MPU and SAL showed decreased plasma FITC-d, oocyte shedding, and lesion scores and higher BWG compared to the IUC birds ( < 0.05). Jejunum , , and - mRNA expression was higher in the IUC compared to the UUC ( < 0.05) group at 5 dpi. At 12 dpi, the birds fed MPU or SAL had lower plasma FITC-d and jejunum - and -10 mRNA expression compared to the IUC birds ( < 0.05). This study indicates that MPU supports intestinal integrity and mucosal immune responses during the peak and recovery phases of infection, which may lead to improved health and performance.
PubMed: 38929356
DOI: 10.3390/ani14121737 -
ImmunoHorizons Jun 2024The underlying contribution of immune complexes in modulating adaptive immunity in mucosal tissues remains poorly understood. In this report, we examined, in mice, the...
The underlying contribution of immune complexes in modulating adaptive immunity in mucosal tissues remains poorly understood. In this report, we examined, in mice, the proinflammatory response elicited by intranasal delivery of the biothreat agent ricin toxin (RT) in association with two toxin-neutralizing mAbs, SylH3 and PB10. We previously demonstrated that ricin-immune complexes (RICs) induce the rapid onset of high-titer toxin-neutralizing Abs that persist for months. We now demonstrate that such responses are dependent on CD4+ T cell help, because treatment of mice with an anti-CD4 mAb abrogated the onset of RT-specific Abs following intranasal RICs exposure. To define the inflammatory environment associated with RIC exposure, we collected bronchoalveolar lavage fluid (BALF) and sera from mice 6, 12, and 18 h after they had received RT or RICs by the intranasal route. A 32-plex cytometric bead array revealed an inflammatory profile elicited by RT that was dominated by IL-6 (>1500-fold increase in BALF) and secondarily by KC (CXCL1), G-CSF, GM-CSF, and MCP-1. RICs induced inflammatory profiles in both BALF and serum response that were similar to RT, albeit at markedly reduced levels. These results demonstrate that RICs retain the capacity to induce local and systemic inflammatory cytokines/chemokines that, in turn, may influence Ag sampling and presentation in the lung mucosa and draining lymph nodes. A better understanding of the fate of immune complexes following intranasal delivery has implications for the development of mucosal vaccines for biothreats and emerging infectious diseases.
Topics: Animals; Administration, Intranasal; Ricin; Mice; Bronchoalveolar Lavage Fluid; Female; Antigen-Antibody Complex; Antibodies, Neutralizing; Immunization; Inflammation; Antibodies, Monoclonal; Cytokines; CD4-Positive T-Lymphocytes; Mice, Inbred BALB C; Mice, Inbred C57BL
PubMed: 38922287
DOI: 10.4049/immunohorizons.2400007 -
Communications Biology Jun 2024Innate lymphoid cells (ILCs) are largely tissue-resident, mostly described within the mucosal tissues. However, their presence and functions in the human draining lymph... (Comparative Study)
Comparative Study
Innate lymphoid cells (ILCs) are largely tissue-resident, mostly described within the mucosal tissues. However, their presence and functions in the human draining lymph nodes (LNs) are unknown. Our study unravels the tissue-specific transcriptional profiles of 47,287 CD127 ILCs within the human abdominal and thoracic LNs. LNs contain a higher frequency of CD127 ILCs than in BM or spleen. We define independent stages of ILC development, including EILP and pILC in the BM. These progenitors exist in LNs in addition to naïve ILCs (nILCs) that can differentiate into mature ILCs. We define three ILC1 and four ILC3 sub-clusters in the LNs. ILC1 and ILC3 subsets have clusters with high heat shock protein-encoding genes. We identify previously unrecognized regulons, including the BACH2 family for ILC1 and the ATF family for ILC3. Our study is the comprehensive characterization of ILCs in LNs, providing an in-depth understanding of ILC-mediated immunity in humans.
Topics: Humans; Immunity, Innate; Lymph Nodes; Lymphocytes; Spleen; Transcriptome; Bone Marrow; Gene Expression Profiling; Male
PubMed: 38918571
DOI: 10.1038/s42003-024-06450-9 -
Microbiology Spectrum Jun 2024infections are getting increasingly serious as antimicrobial resistance spreads. Phage therapy may be a solution to the problem, especially if improved by current...
infections are getting increasingly serious as antimicrobial resistance spreads. Phage therapy may be a solution to the problem, especially if improved by current advances on phage-host studies. As a mucosal pathogen, we hypothesize that and its phages are linked to the bacteriophage adherence to mucus (BAM) model. This means that phage-host interactions could be influenced by mucin presence, impacting the success of phage infections on the host and consequently leading to the protection of the metazoan host. By using a group of four different phages, we tested three important phenotypes associated with the BAM model: phage binding to mucin, phage growth in mucin-exposed hosts, and the influence of mucin on CRISPR immunity of the bacterium. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. Improved phage growth was likely the result of phage exploitation of mucin-induced physiological changes in the host. We could not detect CRISPR activity in our system but identified two putative anti-CRISPR proteins coded by the phage. Overall, the differential responses seen for the phages tested show that the same bacterial species can be targeted by mucosal-associated phages or by phages not affected by mucus presence. In conclusion, the BAM model is relevant for phage-bacterium interactions in , opening new possibilities to improve phage therapy against this important pathogen by considering mucosal interaction dynamics.IMPORTANCESome bacteriophages are involved in a symbiotic relationship with animals, in which phages held in mucosal surfaces protect them from invading bacteria. is one of the many bacterial pathogens threatening humankind during the current antimicrobial resistance crisis. Here, we have tested whether and its phages are affected by mucosal conditions. We discovered by using a collection of four phages that, indeed, mucosal interaction dynamics can be seen in this model. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. These results link and its phages to the bacteriophage adherence to the mucus model and open opportunities to explore this to improve phage therapy, be it by exploiting the phenotypes detected or by actively selecting mucosal-adapted phages for treatment.
PubMed: 38912817
DOI: 10.1128/spectrum.03520-23 -
Mucosal Immunology Jun 2024Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious...
Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious disease immunity. Following acute and chronic infections, Tregs can restrict pathogen-specific T cell responses to limit immunopathology. However, it is unclear if Tregs mediate control of pathology and immunity in distal tissue sites during localized infections. We investigated a role for Tregs in immunity and disease in various tissue compartments in the context of "mild" vaginal Zika virus (ZIKV) infection. We found that Tregs are critical to generate robust virus-specific CD8 T cell responses in the initial infection site. Further, Tregs limit inflammatory cytokines and immunopathology during localized infection; a dysregulated immune response in Treg-depleted mice leads to increased T cell infiltrates and immunopathology in both the vagina and the central nervous system (CNS). Importantly, these CNS infiltrates are not present at the same magnitude during infection of Treg sufficient mice, in which there is not CNS immunopathology. Our data suggest that Tregs are necessary to generate a robust virus-specific response at the mucosal site of infection, while Treg-mediated restriction of bystander inflammation limits immunopathology both at the site of infection as well as distal tissue sites.
PubMed: 38908483
DOI: 10.1016/j.mucimm.2024.06.007 -
Poultry Science Jun 2024Mycoplasma gallisepticum (MG) can cause chronic respiratory disease (CRD) in chickens, which has a significant negative economic impact on the global poultry sector....
Mycoplasma gallisepticum (MG) can cause chronic respiratory disease (CRD) in chickens, which has a significant negative economic impact on the global poultry sector. Respiratory flora is the guardian of respiratory health, and its disorder is closely related to respiratory immunity and respiratory diseases. As a common probiotic in the chicken respiratory tract, Lactobacillus salivarius (L. salivarius) has potential antioxidant, growth performance enhancing, and anti-immunosuppressive properties. However, the specific mechanism through which L. salivarius protects against MG infection has not yet been thoroughly examined. This study intends to investigate whether L. salivarius could reduce MG-induced tracheal inflammation by modulating the respiratory microbiota and metabolites. The results indicated that L. salivarius reduced MG colonization significantly and alleviated the anomalous morphological changes by using the MG-infection model. L. salivarius also reduced the level of Th1 cell cytokines, increased the level of Th2 cell cytokines, and ameliorated immune imbalance during MG infection. In addition, L. salivarius improved the mucosal barrier, heightened immune function, and suppressed the Janus kinase/Signal transducer, and activator of transcription (JAK/STAT) signaling pathway. Notably, MG infection changed the composition of the respiratory microbiota and metabolites, and L. salivarius therapy partially reversed the aberrant respiratory microbiota and metabolite composition. Our results highlighted that these findings demonstrated that L. salivarius played a role in MG-mediated inflammatory damage and demonstrated that L. salivarius, by altering the respiratory microbiota and metabolites, could successfully prevent MG-induced inflammatory injury in chicken trachea.
PubMed: 38908119
DOI: 10.1016/j.psj.2024.103942 -
BMC Nephrology Jun 2024IgA nephropathy, presently recognized as the foremost primary glomerular disorder, emerges as a principal contributor to renal failure globally, with its pathogenesis... (Review)
Review
IgA nephropathy, presently recognized as the foremost primary glomerular disorder, emerges as a principal contributor to renal failure globally, with its pathogenesis yet to be fully elucidated. Extensive research has highlighted the critical role of gut microbiome in the onset and progression of IgA nephropathy, underscoring its importance in accurately delineating the disease's etiology. For example, gut microbiome dysbacteriosis can lead to the production of nephritogenic IgA1 antibodies, which form immune complexes that deposit in the kidneys, causing inflammation and damage. The gut microbiome, a source of numerous bioactive compounds, interacts with the host and plays a regulatory role in gut-immune axis modulation, earning it the moniker of the "second brain." Recent investigations have particularly emphasized a significant correlation between IgA nephropathy and gut microbiome dysbacteriosis. This article offers a detailed overview of the pathogenic mechanisms of IgA nephropathy, specifically focusing on elucidating how alterations in the gut microbiome are associated with anomalies in the intestinal mucosal system in IgA nephropathy. Additionally, it describes the possible influence of gut microbiome on recurrent IgA nephropathy following kidney transplantation. Furthermore, it compiles potential therapeutic interventions, offering both theoretical and practical foundations for the management of IgA nephropathy. Lastly, the challenges currently faced in the therapeutic approaches to IgA nephropathy are discussed.
Topics: Glomerulonephritis, IGA; Humans; Gastrointestinal Microbiome; Dysbiosis; Immunity, Mucosal; Intestinal Mucosa; Kidney Transplantation
PubMed: 38907188
DOI: 10.1186/s12882-024-03646-3