Abstract
Appropriate dendritic cell processing of the microbiota promotes intestinal homeostasis and protects against aberrant inflammatory responses. Mucosal CD103+ dendritic cells are able to produce retinoic acid from retinal, however their role in vivo and how they are influenced by specific microbial species has been poorly described. Bifidobacterium infantis 35624 (B. infantis) feeding to mice resulted in increased numbers of CD103+retinaldehyde dehydrogenase (RALDH)+ dendritic cells within the lamina propria (LP). Foxp3+ lymphocytes were also increased in the LP, while TH1 and TH17 subsets were decreased. 3,7-dimethyl-2,6-octadienal (citral) treatment of mice blocked the increase in CD103+RALDH+ dendritic cells and the decrease in TH1 and TH17 lymphocytes, but not the increase in Foxp3+ lymphocytes. B. infantis reduced the severity of DSS-induced colitis, associated with decreased TH1 and TH17 cells within the LP. Citral treatment confirmed that these effects were RALDH mediated. RALDH+ dendritic cells decreased within the LP of control inflamed animals, while RALDH+ dendritic cells numbers were maintained in the LP of B. infantis-fed mice. Thus, CD103+RALDH+ LP dendritic cells are important cellular targets for microbiota-associated effects on mucosal immunoregulation.
Highlights
The mammalian gastrointestinal microbiota is required for optimal host development and ongoing immune homeostasis [1,2,3]
We demonstrate that B. infantis feeding to mice results in increased CD103+retinaldehyde dehydrogenase (RALDH)+ dendritic cells within the mucosa, which are responsible for the suppression of TH1 and TH17 lymphocytes and amelioration of dextran sulfate sodium (DSS)-induced colitis
In order to determine whether B. infantis was sampled by dendritic cells from either site, CFSE-labelled bacteria were gavaged to mice and single cell suspensions were generated from ileal lamina propria (LP) and Peyer’s patches (PP) after 2 hours
Summary
The mammalian gastrointestinal microbiota is required for optimal host development and ongoing immune homeostasis [1,2,3]. The composition and metabolic activity of the microbiota has profound effects on proinflammatory activity and the induction of immune tolerance by influencing a broad range of mucosal cell types including epithelial cells, dendritic cells, iNKT cells and T lymphocyte subset activity [4,5,6]. Dendritic cell-derived retinoic acid has dramatic effects on dendritic cell activity and lymphocyte subset plasticity. The promotion of TH17 versus Treg phenotypes may be related to the local concentration of retinoic acid, the dendritic cell subset secreting retinoic acid, the local level of proinflammatory mediators and TGF-b, concomitant toll-like receptor activation or induction of specific microRNA [11,12,13,14]. The role of specific microbial species in influencing retinoic acid metabolism and CD103+RALDH+ dendritic cells in vivo has been poorly understood
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