Differential requirements of MyD88 and TRIF pathways in TLR4-mediated immune responses in murine B cells

被引：24

作者：

Yanagibashi, Tsutomu ^{[1
,2
]}

Nagai, Yoshinori ^{[1
,3
]}

Watanabe, Yasuharu ^{[1
]}

Ikutani, Masashi ^{[1
]}

Hirai, Yoshikatsu ^{[1
]}

Takatsu, Kiyoshi ^{[1
,2
]}

机构：

[1] Toyama Univ, Grad Sch Med & Pharmaceut Sci Res, Dept Immunobiol & Pharmacol Genet, Toyama 9300194, Japan

[2] Toyama Prefectural Inst Pharmaceut Res, Imizu, Toyama 9390363, Japan

[3] PRESTO, JST, Kawaguchi, Saitama 3320012, Japan

来源：

IMMUNOLOGY LETTERS | 2015年 / 163卷 / 01期

基金：

日本学术振兴会;

关键词：

CSR; IL-4; Innate immunity; LPS; MyD88; TLR; TRIF; SWITCH DNA RECOMBINATION; TOLL-LIKE RECEPTORS; CUTTING EDGE; LIPOPOLYSACCHARIDE; INDUCTION; TLR4; PROLIFERATION; EXPRESSION; ANTIBODY; COMPLEX;

D O I：

10.1016/j.imlet.2014.11.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

LPS stimulates the TLR4/Myeloid differentiation protein-2 (MD-2) complex and promotes a variety of immune responses in B cells. TLR4 has two main signaling pathways, MyD88 and Toll/IL-1R (TIR)-domain-containing adaptor-inducing interferon-beta (TRIF) pathways, but relatively few studies have examined these pathways in B cells. In this study, we investigated MyD88- or TRIF-dependent LPS responses in B cells by utilizing their knockout mice. Compared with wild-type (WT) B cells, MyD88(-/-) B cells were markedly impaired in up-regulation of CD86 and proliferation induced by lipid A moiety of LPS. TRIF-/- B cells were also impaired in these responses compared with WT B cells, but showed better responses than MyD88(-/-) B cells. Regarding class switch recombination (CSR) elicited by lipid A plus IL-4, MyD88(-/-) B cells showed similar patterns of CSR to WT B cells. However, TRIF-/- B cells showed the impaired in the CSR. Compared with WT and MyD88-/- B cells, TRIF-/- B cells exhibited reduced cell division, fewer. IgG1(+) cells per division, and decreased activation-induced cytidine deaminase (Aicda) mRNA expression in response to lipid A plus IL-4. Finally, IgG1 production to trinitrophenyl (TNP)-LPS immunization was impaired in TRIF-/- mice, while MyD88(-/-) mice exhibited increased IgG1 production. Thus, MyD88 and TRIF pathways differently regulate TLR4-induced immune responses in B cells. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：22 / 31

页数：10

共 39 条

[1] Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].