Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M

Speaker: 陳美君                            Time: 13:10~14:00, Oct.11, 2006

Commentator: 徐麗君 老師                  Place: Room 601

Abstract:

     During the late phase of sepsis, a high percentage of patients are susceptible to infections that results in the increased mortality. Bacterial pneumonia are common in the secondary nosocomial infections. Evidence showed that innate immune cells including macrophages, monocytes and neutrophils are dysfunction in sepsis patients or animals (1). In this seminar paper, the authors usedmurine cecal ligation and puncture (CLP) model of peritonitis-induced sepsis to investigated the role of the TLR4 in sepsis-induced suppression (2). In sublethal CLP model, they found that the mRNA and cell-surface expression of TLR4 remained unchanged in lung after challenging with Pseudomonas aeruginosa. They further examined the expression of downstream regulators in LPS/TLR4 signaling pathway. Neither mRNA nor protein levels of IRAK-1 ( IL-1 receptor–associated kinase–1) and IRAK-4 were altered in lung macrophages. Interestingly, the mRNA and protein levels of the monocyte/macrophage-specific negative regulator IRAK-M were increased after CLP treatment (3). The production of TNF-a and IL-12 was significant increased in thealveolar macrophages of IRAK-M^–/– mice challenged with LPS following CLP, as compared with WT mice. In addition, following CLP and subsequent intrapulmonary gram-negative bacterial challenge, IRAK-M^–/– mice showed higher survival rate, lower bacteria numbers in blood and lung, and higher inflammation cytokine production, neutrophil numbers and myeloperoxidase activities in lung. Taken together, these results indicates that IRAK-M is an important regulator in sepsis-induced immunosuppresion.

References:

1.          Nelson, S. et al. 1990. Endotoxin-induced suppression of lung host defensed. J. Med. 21: 85-103.

2.          Deng , J. C. et al. 2006. Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. J. Clin. Invest. 116: 2532-2542.

3.          Liwe, F. Y. et al. 2005. Negative regulation of Toll-like receptor-mediated immune responses. Nat. Rev. Immunol. 5: 446-458.