Suppression of experimental colitis by intestinal mononuclear phagocytes

Abstract

The contribution of innate immunity to inflammatory bowel disease (IBD) remains an area of intense interest. Macrophages (MØ) and dendritic cells (DC) are considered important factors in regulating the onset of IBD. The goal of this study was to determine if intestinal mononuclear phagocytes (iMNP) serve a pathological or protective role in dextran sulfate sodium (DSS)-induced colitis in mice. Using a conditional MØ/DC depletion transgenic mouse line--MØ Fas-induced apoptosis--to systemically deplete iMNP, DSS colitis histopathology was shown to be more severe in MØ/DC-depleted compared with MØ/DC-intact mice. Similarly, localized iMNP depletion by clodronate-encapsulated liposomes into C57BL/6, BALB/c, and CB.17/SCID mice also increased DSS colitis severity, as indicated by increased histopathology, weight loss, rectal bleeding, decreased stool consistency, and colon length compared with MØ/DC-intact, DSS-treated mice. Histology revealed that iMNP depletion during DSS treatment led to increased neutrophilic inflammation, increased epithelial injury, and enhanced mucin depletion from Goblet cells. iMNP depletion did not further elevate DSS-induced expression of TNF-alpha and IFN-gamma mRNA but significantly increased expression of CXCL1 chemokine mRNA. Myeloperoxidase activity was increased in colons of MØ/DC-depleted, DSS-treated mice, compared with DSS alone, coincident with increased neutrophil infiltration in diseased colons. Neutrophil depletion combined with MØ/DC depletion prevented the increase in DSS colitis severity compared with MØ/DC depletion alone. This study demonstrates that iMNP can serve a protective role during development of acute colitis and that protection is associated with MØ/DC-mediated down-regulation of neutrophil infiltration.

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

“…52 The reduction in cellular infiltration observed in the present study was associated with a decrease in colon damage. It has been suggested that the inhibition of migratory mononuclear cells, 55 but not resident cells, 56 ameliorates colitis. Similarly, the infiltration of neutrophils into the colonic mucosa is believed to play a key role in mediating tissue damage and the clinical symptoms in experimental colitis.…”

Immunity to gastrointestinal nematode infections

“…75,192,203,204 Furthermore, macrophages in the intestinal mucosa are also likely to play an important role in tissue repair, as has been shown in various settings of inflammation. [205][206][207][208][209][210] Whereas most research on host-parasite interactions has focused on the underlying factors that govern resistance and susceptibility, the long-term consequences of both acute and chronic worm infections are largely unexplored. Given the inverse correlation between parasite exposure and the occurrence of immune-associated disorders, it is quite surprising that so little attention has been devoted to this subject, particularly in the case of Trichuris infections that have been in clinical trial for the treatment of various inflammatory disorders.…”

CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells

“…The clinical scoring of a Disease Activity Index (DAI) for DSS induced colitis was based on weight loss, stool consistency, and bleeding, as previously described (32,33). The DAI was scored 0-4 for each parameter per mouse and then averaged for each group.…”