CD103+ dendritic cells (DCs) are the major conventional DC population in the intestinal lamina propria (LP). Our previous report showed that a small number of cells in the LP could be classified into four subsets based on the difference in CD11c/CD11b expression patterns: CD11chiCD11blo DCs, CD11chiCD11bhi DCs, CD11cintCD11bint macrophages, and CD11cintCD11bhi eosinophils. The CD11chiCD11bhi DCs, which are CD103+, specifically express TLR5 and induce the differentiation of naive B cells into IgA+ plasma cells. These DCs also mediate the differentiation of Ag-specific Th17 and Th1 cells in response to flagellin. We found that small intestine CD103+ DCs of the LP (LPDCs) could be divided into a small subset of CD8α+ cells and a larger subset of CD8α− cells. Flow cytometry analysis revealed that CD103+CD8α+ and CD103+CD8α− LPDCs were equivalent to CD11chiCD11blo and CD11chiCD11bhi subsets, respectively. We analyzed a novel subset of CD8α+ LPDCs to elucidate their immunological function. CD103+CD8α+ LPDCs expressed TLR3, TLR7, and TLR9 and produced IL-6 and IL-12p40, but not TNF-α, IL-10, or IL-23, following TLR ligand stimulation. CD103+CD8α+ LPDCs did not express the gene encoding retinoic acid-converting enzyme Raldh2 and were not involved in T cell-independent IgA synthesis or Foxp3+ regulatory T cell induction. Furthermore, CD103+CD8α+ LPDCs induced Ag-specific IgG in serum, a Th1 response, and CTL activity in vivo. Accordingly, CD103+CD8α+ LPDCs exhibit a different function from CD103+CD8α− LPDCs in active immunity. This is the first analysis, to our knowledge, of CD8α+ DCs in the LP of the small intestine.
Patient with recurrent Clostridioides difficile infection Fecal microbiota transplantation Before After Gammaproteobacteria Caudovirales Bacteroidia Clostridia Success Microviridae Donor 1.Metagenome analysis; Compositional changes of bacteriome and virome 2.Prophage-and CRISPR-based bacteria-phage association analysis; Host-parasite dynamics 3.Gene pathway analysis; Functional restoration of microbiome BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT. METHODS: The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophagebased and CRISPR spacer-based host bacteria-phage
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