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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. [ABSTRACT FROM AUTHOR]

Background: Major histocompatibility complex (MHC) class II molecules play crucial roles in immune activation by presenting foreign peptides to antigen-specific T helper cells and thereby inducing adaptive immune responses. Although adaptive immunity is a highly effective defense system, it takes several days to become fully operational and needs to be triggered by danger-signals generated during the preceding innate immune response. Here we show that MHC class II molecules synergize with Toll-like receptor (TLR) 2 and TLR4 in inducing an innate immune response. Methodology/Principal Findings: We found that co-expression of MHC class II molecules and TLR2 or TLR4 in human embryonic kidney (HEK) cells 293 leads to enhanced production of the anti-microbial peptide human-β-defensin (hBD) 2 after treatment with TLR2 stimulus bacterial lipoprotein (BLP) or TLR4 ligand lipopolysaccharide (LPS), respectively. Furthermore, we found that peritoneal macrophages of MHC class II knock-out mice show a decreased responsiveness to TLR2 and TLR4 stimuli compared to macrophages of wild-type mice. Finally, we show that MHC class II molecules are physically and functionally associated with TLR2 in lipid raft domains of the cell membrane. Conclusions/Significance: These results demonstrate that MHC class II molecules are, in addition to their central role in adaptive immunity, also implicated in generating optimal innate immune responses. [ABSTRACT FROM AUTHOR]

Children of farmers are at decreased risk of developing allergies. Results of epidemiological studies suggest increased exposure to microbial compounds might be responsible for this reduced risk. Alterations in adaptive immune response are thought to be the underlying mechanism. We measured expression of receptors for microbial compounds known to trigger the innate immune response. We showed that blood cells from farmers' children express significantly higher amounts of CD14 (0.96 vs 0.43, p=0.0013), and Toll-like receptor 2 (0.11 vs 0.04, p<0.0001) than those from non-farmers' children. We propose that the innate immune system responds to the microbial burden in the environment and modulates the development of allergic disease. [ABSTRACT FROM AUTHOR]