Induction of gamma interferon production in human alveolar macrophages by Mycobacterium tuberculosis

被引:172
作者
Fenton, MJ
Vermeulen, MW
Kim, S
Burdick, M
Strieter, RM
Kornfeld, H
机构
[1] MASSACHUSETTS GEN HOSP,PULM RES LAB,CHARLESTOWN,MA 02129
[2] UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,ANN ARBOR,MI 48109
关键词
D O I
10.1128/IAI.65.12.5149-5156.1997
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Gamma interferon (IFN-gamma) is a cytokine which plays a critical role in resistance to Mycobacterium tuberculosis infection. While T lymphocytes and natural killer cells are a major source of IFN-gamma, previous demonstrations that it can be produced by murine macrophages prompted us to examine the capacity of human alveolar macrophages to express IFN-gamma. Here we report that in vitro infection of alveolar macrophages with M. tuberculosis induces both the release of IFN-gamma protein and a transient increase in IFN-gamma mRNA levels, The IFN-producing cells were shown to be macrophages by reverse transcription-in situ PCR We also observed that M. tuberculosis stimulation resulted in IFN-gamma-dependent expression of the chemokines IFN-gamma-inducible protein 10 and monokine induced by IFN-gamma, suggesting that macrophage-derived IFN-gamma can function in an autocrine and/or paracrine manner, The existence of a positive regulatory loop was suggested by the observation that exogenous IFN-gamma protein could induce IFN-gamma mRNA expression in uninfected alveolar macrophages. Interleukin-12, was also found to be a potent inducer of IFN-gamma production, and M. tuberculosis-induced IFN-gamma production appears to be mediated, at least in part, by IL-12. In contrast, M. tuberculosis-induced IFN-gamma production by alveolar macrophages could be blocked by exogenous interleukin-10. These studies are the first to demonstrate an autoregulatory role for IFN-gamma produced by alveolar macrophages infected in vitro with M. tuberculosis.
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收藏
页码:5149 / 5156
页数:8
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