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Infect. Immun., Dec 1997, 5149-5156, Vol 65, No. 12
Copyright © 1997, American Society for Microbiology

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

MJ Fenton, MW Vermeulen, S Kim, M Burdick, RM Strieter and H Kornfeld
Pulmonary Center, Boston University School of Medicine, Massachusetts 02118, USA. mfenton@bupula.bu.edu

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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