Gut Microbiota Modulation on Intestinal Mucosal Adaptive Immunity

Wang, Li; Zhu, Limeng; Qin, Song

doi:10.1155/2019/4735040

Cited by 96 publications

(81 citation statements)

References 110 publications

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“…Thus, oral fungal challenge with the commonly used laboratory C. albicans strain SC5314 generates an acute immune response in a naive host (13). Since the adaptive immunity plays a critical role in maintaining immune tolerance toward commensal organisms, such as commensal C. albicans, understanding its relationship with fungi is critical (14). In an adaptive immunity OPC rechallenge model using a derivate of the pathogenic C. albicans strain SC5314, CD4 + Th17 cells protect from mucosal Candida infection but can be compensated by other IL-17-producing cells in CD4-deficient hosts (15,16).…”

Section: Introductionmentioning

confidence: 99%

Mucosal IgA Prevents Commensal Candida albicans Dysbiosis in the Oral Cavity

2020

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The fungus Candida albicans colonizes the oral mucosal surface of 30-70% of healthy individuals. Due to local or systemic immunosuppression, this commensal fungus is able to proliferate resulting in oral disease, called oropharyngeal candidiasis (OPC). However, in healthy individuals C. albicans causes no harm. Unlike humans mice do not host C. albicans in their mycobiome. Thus, oral fungal challenge generates an acute immune response in a naive host. Therefore, we utilized C. albicans clinical isolates which are able to persist in the oral cavity without causing disease to analyze adaptive responses to oral fungal commensalism. We performed RNA sequencing to determine the transcriptional host response landscape during C. albicans colonization. Pathway analysis revealed an upregulation of adaptive host responses due to C. albicans oral persistence, including the upregulation of the immune network for IgA production. Fungal colonization increased cross-specific IgA levels in the saliva and the tongue, and IgA + cells migrated to foci of fungal colonization. Binding of IgA prevented fungal epithelial adhesion and invasion resulting in a dampened proinflammatory epithelial response. Besides CD19 + CD138 − B cells, plasmablasts, and plasma cells were enriched in the tongue of mice colonized with C. albicans suggesting a potential role of B lymphocytes during oral fungal colonization. B cell deficiency increased the oral fungal load without causing severe OPC. Thus, in the oral cavity B lymphocytes contribute to control commensal C. albicans carriage by secreting IgA at foci of colonization thereby preventing fungal dysbiosis.

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Section: Introductionmentioning

confidence: 99%

Mucosal IgA Prevents Commensal Candida albicans Dysbiosis in the Oral Cavity

2020

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“…Hence, IETs are critical in balancing immune tolerance and protection within the intestinal tract. Moreover, microbial and dietary antigen exposure majorly influence the development, specificity, reactivity, and homeostasis of IETs (6,(10)(11)(12)(13)(14), largely contributing to their fate in promoting or deteriorating intestinal health (2).…”

Section: Introductionmentioning

confidence: 99%

Intraepithelial T cells diverge by intestinal location as pigs age

Wiarda

Trachsel

Bond

et al. 2020

Preprint

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T cells resident within the intestinal epithelium play a central role in barrier integrity and provide a first line of immune defense. Intraepithelial T cells (IETs) are among the earliest immune cells to populate and protect intestinal tissues, thereby giving them an important role in shaping gut health early in life. In pigs, IETs are poorly defined, and their maturation in young pigs has not been well studied. Given the importance of IETs in contributing to early life and long-term intestinal health through interactions with epithelial cells, the microbiota, and additional environmental factors, a deeper characterization of IETs in pigs is warranted. The objective of this study was to analyze age-and intestinal location-dependent changes in IETs across multiple sites of the small and large intestine in pigs between 4 and 8 weeks of age. IETs increased in abundance over time and belonged to both γδ and αβ T cell lineages. Similar compositions of IETs were identified across intestinal sites in 4-week-old pigs, but compositions diverged between intestinal sites as pigs aged. CD2 + CD8α + γδ T cells and CD4 -CD8α + αβ T cells comprised >78% of total IETs at all intestinal locations and ages examined. Greater percentages of γδ IETs were present in large intestine compared to small intestine in older pigs. Small intestinal tissues had greater percentages of CD2 + CD8αγδ IETs, while CD2 + CD8α + γδ IET percentages were greater in the large intestine. Percentages of CD4 -CD8α + αβ IETs increased over time across all intestinal sites. Moreover, percentages of CD27 + cells decreased in ileum and large intestine over time, indicating increased IET activation as pigs aged. Percentages of CD27 + cells were also higher in small intestine compared to large intestine at later timepoints.Results herein emphasize 4 to 8 weeks of age as a critical window of IET maturation and suggest strong associations between intestinal location and age with IET heterogeneity in pigs.

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“…The overall enhanced tolerogenic DC activity in the intestinal compartment including draining lymph nodes could explain the discrepant intestinal adaptive immunity that established in DC hBcl-2 and WT mice. Indeed Treg, Th17 and sIgA + B cells, all increased in DC hBcl-2 compared to WT mice, are major components of intestinal homeostasis (Li Wang, Zhu, and Qin 2019).…”

Section: Discussionmentioning

confidence: 99%

Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases

Lécuyer

Roy

Gestin

et al. 2020

Preprint

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Excess of chronic contact between microbial motifs and intestinal immune cells are known to trigger a low-grade inflammation involved in many pathologies such as obesity and diabetes. The important skewing of intestinal adaptive immunity in the context of diet-induced obesity (DIO) is well described but how dendritic cells (DCs) participate to these changes is still poorly documented. To address this question, transgenic mice with enhanced DCs lifespan and immunogenicity (DChBcl-2 mice), are challenged with a high fat diet. Those mice display resistance to DIO and metabolic alterations. The DIO resistant phenotype is associated with healthier parameters of intestinal barrier function and lower intestinal inflammation. DChBcl-2 DIO-resistant mice demonstrate a particular increase in tolerogenic DC numbers and function which is associated with strong intestinal IgA, Th17 and T regulatory immune responses. Microbiota composition and function analyses reveal that the DChBcl-2 mice microbiota is characterized by a lower immunogenicity and an enhanced butyrate production. Cohousing experiments and fecal microbial transplantations are sufficient to transfer the DIO resistance status to WT mice demonstrating that maintenance of DCs tolerogenic ability sustains a microbiota able to drive DIO resistance. DCs tolerogenic function is revealed as a new potent target in metabolic diseases management.

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Gut Microbiota Modulation on Intestinal Mucosal Adaptive Immunity

Cited by 96 publications

References 110 publications

Mucosal IgA Prevents Commensal Candida albicans Dysbiosis in the Oral Cavity

Mucosal IgA Prevents Commensal Candida albicans Dysbiosis in the Oral Cavity

Intraepithelial T cells diverge by intestinal location as pigs age

Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases

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