Activation of Plasmacytoid Dendritic Cells in Colon-Draining Lymph Nodes during Citrobacter rodentium Infection Involves Pathogen-Sensing and Inflammatory Pathways Distinct from Conventional Dendritic Cells

Abstract

Dendritic cells (DCs) bear the main responsibility for initiation of adaptive immune responses necessary for antimicrobial immunity. In the small intestine, afferent lymphatics convey Ags and microbial signals to mesenteric lymph nodes (LNs) to induce adaptive immune responses against microbes and food Ags derived from the small intestine. Whether the large intestine is covered by the same lymphatic system or represents its own lymphoid compartment has not been studied until very recently. We identified three small mesenteric LNs, distinct from small intestinal LNs, which drain lymph specifically from the colon, and studied DC responses to the attaching and effacing pathogen Citrobacter rodentium in these. Transcriptional profiling of conventional (CD11chighCD103high) DC and plasmacytoid (plasmacytoid DC Ag-1highB220+CD11cint) DC (pDC) populations during steady-state conditions revealed activity of distinct sets of genes in these two DC subsets, both in small intestinal and colon-draining LNs. C. rodentium activated DC especially in colon-draining LNs, and gene expression changed in pDC more profoundly than in conventional DC. Among the genes most upregulated in pDC were C-type lectin receptor CLEC4E, IL-1Rs (IL-1R1 and -2), proinflammatory cytokines (IL-1a and IL-6), and TLR6. Our results indicate that colon immune surveillance is distinct from that of the small intestine in terms of draining LNs, and identify pDC as active sentinels of colonic inflammation and/or microbial dysbiosis.

Low RUNX3 expression alters dendritic cell function in patients with systemic sclerosis and contributes to enhanced fibrosis

“…Furthermore, our observation on an increase of CD86+ pDCs in the inguinal lymph node of bleomycin-treated mice, implied pDC activation in the skin and subsequent migration to the skin draining lymph node. Increased expression of CD86 in pDC in the lymph node has been shown in infection models60 61 and CD80/CD86 deficiency ameliorated skin inflammation in a pDC-dependent imiquimod-induced systemic autoimmune disease model 36…”

Plasmacytoid Dendritic Cells Provide Protection Against Bacterial-Induced Colitis

“…In contrast to their well-established immunoregulatory role during viral infection, little is known about the role of pDCs in bacterial infection. Several studies have shown that pDCs are activated by Citrobacter rodentium (6), Borrelia burgdorferi (7), Toxoplasma gondii (8), and Staphylococcus aureus (9) and produce cytokines including type I IFN and IL-12. Moreover, a recent report showed that mouse pDC express TLR2 which detects polysaccharide A, an immunomodulatory molecule expressed by the gut microbiota Bacteroides fragilis and induces IL-10 production by T regulatory cells (10).…”

The Role of Plasmacytoid Dendritic Cells in Gut Health

“…In addition, the expressions of costimulatory molecules on pDCs are upregulated, contributing to interactions with T cell. The pDCs in the colon-draining LNs during a Citrobacter rodentium infection can be specifically activated, resulting in the production of C-type lectin receptor and proinflammatory cytokines (74).…”