Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-mediated signaling contributes to innate immune responses in the lung during Escherichia coli pneumonia

被引:59
作者
Jeyaseelan, Samithamby
Young, Scott K.
Fessler, Michael B.
Liu, Yuhong
Malcolm, Kenneth C.
Yamamoto, Masahiro
Akira, Shizuo
Worthen, G. Scott
机构
[1] Natl Jewish Med & Res Ctr, Dept Med, Div Resp Infect, Denver, CO 80206 USA
[2] Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA
[3] Osaka Univ, Dept Host Def, Microbial Dis Res Inst, Osaka, Japan
关键词
D O I
10.4049/jimmunol.178.5.3153
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Bacterial pneumonia remains a serious disease and is associated with neutrophil recruitment. Innate immunity is pivotal for the elimination of bacteria, and TLRs are essential in this process. Toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF) is an adaptor for TLR3 and TLR4, and is associated with the MyD88-independent cascade. However, the importance of TRIF in immune responses against pulmonary bacterial pathogens is not well understood. We investigated the involvement of TRIF in a murine model of Escherichia coli pneumonia. TRIF-/- mice infected with E. coli display attenuated neutrophil migration; NF-kappa B activation; and TNF-alpha, IL-6, and LPS-induced C-X-C chemokine production in the lungs. In addition, E. coli-induced phosphorylation of JNK, ERK, and p38 MAPK was detected in bone marrow-derived macrophages (BMMs) of TRIF+/+ mice, but attenuated in BMMs of TRIF-/- mice. Furthermore, E. coli-induced TNF-alpha and IL-6 production was attenuated in BMMs of TRIF-/- mice. E. coli LPS-induced late MAPK activation, and TNF-alpha and IL-6 production were abolished in BMMs of TRIF-/- mice. Moreover, TRIF is not required for LPS-induced neutrophil influx, and keratinocyte cell-derived chemokine, MIP-2, and LPS-induced C-X-C chemokine production in the lungs. Using TLR3(-/-) mice, we ruled out the role of TLR3-mediated TRIF-dependent neutrophil influx during E. coli pneumonia. A TLR4-blocking Ab inhibited E. coli-induced TNF-alpha and IL-6 in BMMs of both TRIF-/- and TRIF+/+ mice, suggesting that TRIF-mediated signaling involves TLR4. We also found that TRIF is critical to control E. coli burden in the lungs and E. coli dissemination. Thus, rapid activation of TRIF-dependent TLR4-mediated signaling cascade serves to augment pulmonary host defense against a Gram-negative pathogen.
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收藏
页码:3153 / 3160
页数:8
相关论文
共 39 条
  • [1] Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function
    Adachi, O
    Kawai, T
    Takeda, K
    Matsumoto, M
    Tsutsui, H
    Sakagami, M
    Nakanishi, K
    Akira, S
    [J]. IMMUNITY, 1998, 9 (01) : 143 - 150
  • [2] Pathogen recognition and innate immunity
    Akira, S
    Uematsu, S
    Takeuchi, O
    [J]. CELL, 2006, 124 (04) : 783 - 801
  • [3] Role of toll-like receptor 4 in gram-positive and gram-negative pneumonia in mice
    Branger, J
    Knapp, S
    Weijer, S
    Leemans, JC
    Pater, JM
    Speelman, P
    Florquin, SR
    van der Poll, T
    [J]. INFECTION AND IMMUNITY, 2004, 72 (02) : 788 - 794
  • [4] TLR2 signaling is critical for Mycoplasma pneumoniae-induced airway mucin expression
    Chu, HW
    Jeyaseelan, S
    Rino, JG
    Voelker, DR
    Wexler, RB
    Campbell, K
    Harbeck, RJ
    Martin, RJ
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 174 (09) : 5713 - 5719
  • [5] Pneumonia in the elderly: Overview of diagnostic and therapeutic approaches
    Fein, AM
    [J]. CLINICAL INFECTIOUS DISEASES, 1999, 28 (04) : 726 - 729
  • [6] A role for hydroxy-methylglutaryl coenzyme a reductase in pulmonary inflammation and host defense
    Fessler, MB
    Young, SK
    Jeyaseelan, S
    Lieber, JG
    Arndt, PG
    Nick, JA
    Worthen, GS
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 171 (06) : 606 - 615
  • [7] Identification of Lps2 as a key transducer of MyD88-independent TIR signalling
    Hoebe, K
    Du, X
    Georgel, P
    Janssen, E
    Tabeta, K
    Kim, SO
    Goode, J
    Lin, P
    Mann, N
    Mudd, S
    Crozat, K
    Sovath, S
    Han, J
    Beutler, B
    [J]. NATURE, 2003, 424 (6950) : 743 - 748
  • [8] Hoshino K, 1999, J IMMUNOL, V162, P3749
  • [9] Toll-IL-1 receptor domain-containing adaptor protein is critical for early lung immune responses against Escherichia coli lipopolysaccharide and viable Escherichia coli
    Jeyaseelan, S
    Manzer, R
    Young, SK
    Yamamoto, M
    Akira, S
    Mason, RJ
    Worthen, GS
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 175 (11) : 7484 - 7495
  • [10] Induction of CXCL5 during inflammation in the rodent lung involves activation of alveolar epithelium
    Jeyaseelan, S
    Manzer, R
    Young, SK
    Yamamoto, M
    Akira, S
    Mason, RJ
    Worthen, GS
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2005, 32 (06) : 531 - 539