IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

被引：26

作者：

Horsnell, W. G. C. ^{[1
]}

Vira, A. ^{[1
]}

Kirstein, F. ^{[1
]}

Mearns, H. ^{[1
]}

Hoving, J. C. ^{[1
]}

Cutler, A. J. ^{[1
]}

Dewals, B. ^{[1
]}

Myburgh, E. ^{[1
]}

Kimberg, M. ^{[1
]}

Arendse, B. ^{[1
]}

White, N. ^{[1
]}

Lopata, A. ^{[1
]}

Burger, P. E. ^{[1
]}

Brombacher, F. ^{[1
]}

机构：

[1] Univ Cape Town, Fac Hlth Sci, Int Ctr Genet Engn & Biotechnol, Inst Infect Dis & Mol Med,Div Immunol, ZA-7925 Cape Town, South Africa

来源：

MUCOSAL IMMUNOLOGY | 2011年 / 4卷 / 01期

基金：

英国医学研究理事会; 新加坡国家研究基金会;

关键词：

LEISHMANIA-MAJOR INFECTION; AIRWAY MUCUS PRODUCTION; INTESTINAL EPITHELIUM; HELMINTH INFECTION; NEMATODE INFECTION; T-LYMPHOCYTES; IL-4; RESPONSES; ACTIVATION; RECEPTOR;

D O I：

10.1038/mi.2010.46

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Nippostrongylus brasiliensis infections generate pulmonary pathologies that can be associated with strong T(H)2 polarization of the host's immune response. We present data demonstrating N. brasiliensis-driven airway mucus production to be dependent on smooth muscle cell interleukin 4 receptor-alpha (IL-4R alpha) responsiveness. At days 7 and 10 post infection (PI), significant airway mucus production was found in IL-4R alpha(-/lox) control mice, whereas global knockout (IL-4R alpha(-/-)) and smooth muscle-specific IL-4R alpha-deficient mice (SM-MHCCre IL-4R alpha(-/lox)) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHCCre IL-4R alpha(-/lox) mice was impaired along with a transient reduction in T-cell numbers in the lung. In vitro treatment of smooth muscle cells with secreted N. brasiliensis excretory -secretory antigen (NES) induced IL-6 production. Decreased protein kinase C (PKC)-dependent smooth muscle cell proliferation associated with cell cycle arrest was found in cells stimulated with NES. Together, these data demonstrate that both IL-4R alpha and NES-driven responses by smooth muscle cells make important contributions in initiating T(H)2 responses against N. brasiliensis infections.

引用

页码：83 / 92

页数：10

共 56 条

[1] Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells [J].