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.

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 inhibiting Th1 and Th17 differentiation of CD4+ T cells. Together, these studies demonstrated that fecal bacteria from CD patients presented enhanced capacity to upregulate pattern-recognition molecules in macrophages, which could be repressed by IL-4.

journal_name

Microb Pathog

journal_title

Microbial pathogenesis

authors

Gu J,Liu G,Xing J,Song H,Wang Z

doi

10.1016/j.micpath.2018.05.009

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

40-44

eissn

0882-4010

issn

1096-1208

pii

S0882-4010(18)30282-1

journal_volume

121

pub_type

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