Plasmacytoid Dendritic Cells Provide Protection Against Bacterial-Induced Colitis

Abstract

We have examined the influence of depleting plasmacytoid dendritic cells (pDC) in mice on the immune response to the gut pathogen Citrobacter rodentium , an organism that is a model for human attaching effacing pathogens such as enterohaemorraghic E. coli . A significantly higher number of C. rodentium were found in mice depleted of pDC from 7 days after infection and pDC depleted mice showed increased gut pathology and higher levels of mRNA encoding inflammatory cytokines in the colon upon infection. pDC-depletion led to a compromising of the gut mucosal barrier that may have contributed to increased numbers of C. rodentium in systemic organs. pDC-depleted mice infected with C. rodentium suffered substantial weight loss necessitating euthanasia. A number of observations suggested that this was not simply the result of dysregulation of immunity in the colon as pDC-depleted mice infected intravenously with C. rodentium also exhibited exacerbated weight loss, arguing that pDC influence systemic immune responses. Overall, these data indicate that pDC contribute at multiple levels to immunity to C. rodentium including control of bacterial numbers in the colon, maintenance of colon barrier function and regulation of immune responses to disseminated bacteria.

Plasmacytoid dendritic cells regulate host immune response to Citrobacter rodentium induced colitis in colon‐draining lymph nodes

“…In pDC‐deficient mice, C. rodentium infection caused a severe colitis, which necessitated to end follow‐up within 5–6 days from infection. This is consistent with lethal infection reported in another study [16], although the appearance of significant weight loss (Fig. 1A), lethargy, and appearance of general indices of colitis (Supporting Information Fig.…”

“…While in WT mice, C. rodentium induces relatively mild and noninvasive infection of colonic mucosa, mice modified genetically may succumb to infection due to impaired host response and invasion of microbes in the body [19–21]. This study corroborates the finding of an earlier study [16] regarding the importance of pDC in controlling C. rodentium infection and related immune response and reveals hitherto unrecognized roles for pDC in controlling local host response in the gut.…”

Cathelicidins Modulate TLR-Activation and Inflammation

“…Plasmacytoid Dendritic Cells (pDCs) pDCs play an important role in many inflammatory processes, which include wound healing, antiviral and antibacterial responses, but also autoinflammatory responses (49,(110)(111)(112)(113). Within all these processes, their main role is the production of high quantities of IFN-α, which is produced upon activation of the endosomally located TLR7 by ssRNA or TLR9 by DNA (113).…”

Mammary tumors alter the fecal bacteriome and permit enteric bacterial translocation

“…Higher splenic bacterial burden is common amongst conditions that induce colonic barrier dysfunction and bacterial translocation, including social stress and infectious colitis in mice [ 34 , 35 ]. Relative to Control, Tumor mice had higher spleen mass (Fig.…”