Systemic Activation of TLR3-Dependent TRIF Signaling Confers Host Defense against Gram-Negative Bacteria in the Intestine

Frontiers in Cellular and Infection Microbiology
Jose RuizMasayuki Fukata

Abstract

Recognition of Gram-negative bacteria by toll-like receptor (TLR)4 induces MyD88 and TRIF mediated responses. We have shown that TRIF-dependent responses play an important role in intestinal defense against Gram-negative enteropathogens. In the current study, we examined underlying mechanisms of how systemic TRIF activation enhances intestinal immune defense against Gram-negative bacteria. First we confirmed that the protective effect of poly I:C against enteric infection of mice with Yersinia enterocolitica was dependent on TLR3-mediated TRIF signaling by using TLR3-deficient mice. This protection was unique in TRIF-dependent TLR signaling because systemic stimulation of mice with agonists for TLR2 (Pam3CSK4) or TLR5 (flagellin) did not reduce mortality on Y. enterocolitica infection. Systemic administration of poly I:C mobilized CD11c+, F4/80+, and Gr-1(hi) cells from lamina propria and activated NK cells in the mesenteric lymph nodes (MLN) within 24 h. This innate immune cell rearrangement was type I IFN dependent and mediated through upregulation of TLR4 followed by CCR7 expression in these innate immune cells found in the intestinal mucosa. Poly I:C induced IFN-γ expression by NK cells in the MLN, which was mediated throug...Continue Reading

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Citations

May 4, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danish SalehAlexei Degterev
Apr 16, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rongrong LaiXiaojian Wang
May 3, 2018·Cell Death & Disease·Marta Monguió-TortajadaFrancesc E Borràs
Sep 28, 2017·International Journal of Molecular Medicine·Hongjun BianJianni Qi
Jan 29, 2019·Frontiers in Cellular and Infection Microbiology·Grasielle Pereira JannuzziKaren Spadari Ferreira

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Methods Mentioned

BETA
lavage
FACS
ELISA
PCR

Software Mentioned

GraphPad Prism

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