Branger Judith, Leemans Jaklien C, Florquin Sandrine, Weijer Sebastiaan, Speelman Peter, Van Der Poll Tom
Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Int Immunol. 2004 Mar;16(3):509-16. doi: 10.1093/intimm/dxh052.
Toll-like receptors (TLR) play an essential role in the innate recognition of microorganisms by the host. To determine the role of TLR4 in host defense against lung tuberculosis, TLR4 mutant (C3H/HeJ) and wild-type (C3H/HeN) mice were intranasally infected with live Mycobacterium tuberculosis. TLR4 mutant mice were more susceptible to pulmonary tuberculosis, as indicated by a reduced survival and an enhanced mycobacterial outgrowth. Lung infiltrates were more profound in TLR4 mutant mice and contained more activated T cells. Splenocytes of infected TLR4 mutant mice demonstrated a reduced capacity to produce the protective type 1 cytokine IFN-gamma upon antigen-specific stimulation, indicating that TLR4 may be involved in the generation of acquired T cell-mediated immunity. These data suggest that TLR4 plays a protective role in host defense against lung infection by M. tuberculosis.
Toll样受体（TLR）在宿主对微生物的天然识别中发挥着至关重要的作用。为了确定TLR4在宿主抗肺结核防御中的作用，将TLR4突变体（C3H/HeJ）和野生型（C3H/HeN）小鼠经鼻内感染活的结核分枝杆菌。TLR4突变体小鼠对肺结核更易感，表现为生存率降低和分枝杆菌生长增强。TLR4突变体小鼠的肺部浸润更严重，且含有更多活化的T细胞。感染的TLR4突变体小鼠的脾细胞在抗原特异性刺激后产生保护性1型细胞因子IFN-γ的能力降低，表明TLR4可能参与获得性T细胞介导免疫的产生。这些数据表明，TLR4在宿主抗结核分枝杆菌肺部感染防御中发挥着保护作用。
