Fecal bacteria from Crohn's disease patients more potently activated NOD-like receptors and Toll-like receptors in macrophages, in an IL-4-repressible fashion

Microbial Pathogenesis
Jun GuZhongchuan Wang

Abstract

Crohn's disease (CD) is characterized by a pathogenic intestinal inflammation mediated by a Th1-skewed immune system and a dysregulated intestinal mucosal community. In this study, we investigated the role of bacteria on the activation and function of monocytes, and its association with CD pathogenesis. To this end, fecal bacteria from CD patients and healthy controls were collected and used to stimulate autologous circulating monocytes. Fecal bacteria from CD patients were more effective at upregulating NOD2, NLRP3, TLR2, and TLR4 expression than fecal bacteria from healthy controls. Furthermore, the monocyte-derived macrophages (MDMs) induced by CD bacteria were more sensitive to E. coli stimulation than the MDMs induced by control bacteria, and demonstrated more M1 characteristics with high IL-6, TNF-α, and IL-12 and low IL-4 production. These effects mediated by fecal bacteria from CD patients could be repressed by the supplementation of IL-4. IL-4 not only suppressed the expression of NOD1, NOD2, NLRP3, TLR2, TLR4, and CD14 in MDMs induced by CD bacteria, but also suppressed E. coli-mediated expression of IL-6, TNF-α, and IL-12. Furthermore, IL-4-conditioned MDMs were more effective at supporting Th2 differentiation and in...Continue Reading

Citations

Oct 11, 2019·The Journal of Biological Chemistry·Su-Ho ParkTae Sung Kim
Nov 5, 2020·International Journal of Molecular Sciences·Kohei Wagatsuma, Hiroshi Nakase

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