Macrophage migration inhibitory factor-2 of Wuchereria bancrofti suppressed the DSS-induced colitis in a mouse model by promoting alternative activation of peritoneal macrophages and increasing the number of Treg cells in the colon

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Abstract In this study, we cloned the homologue of macrophage migration inhibitory factor (MIF) secreted by the human filarial parasite Wuchereria bancrofti (rWbaMIF-2) and evaluated its potential in ameliorating inflammation in a dextran sulfate sodium salt (DSS)-induced colitis model. DSS administration resulted in substantial loss of body weight along with bloody diarrhea, severe inflammation in the colon and reduced length of the colon in just under 7 days. Treatment with rWbaMIF-2 reversed the clinical symptoms in DSS administered mice, characterized by no blood in the stools, minimal inflammation on the colon wall and the mice maintained normal colon length. rWbaMIF-2 treatment downregulated TNF-α, IL-6, IFN-γ, IL-1β, IL-17A, and NOS2 genes in the colon tissue and upregulated the percentage of IL-10 producing Treg and B1 cells in the colon and peritoneal cavity. Thus, one of the mechanisms by which rWbaMIF-2 induce its anti-inflammatory effect appeared to be by promoting the infiltration of IL-10 producing Treg cells into the colon. Further analysis showed alternative activation of F4/80+ large peritoneal macrophages (LPMs) with increased expression of arginase (p≤0.05) and reduced expression of iNOS, MPO activity, TNF-α, IL-6 and TLR4 in LPMs following rWbaMIF-2 treatment. Thus, for the first time, we demonstrate here that rWbaMIF-2 treatment can activate LMP macrophages alternatively and promote infiltration of Treg cells into the colon to suppress inflammation in a colitis model. These studies also demonstrate the potential of developing rWbaMIF-2 as a small molecule therapeutic agent for colitis and other inflammatory conditions. Studies funded by NIH RO1 AI116441.

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