Interferon-γ-activated human monocytes inhibit the intracellular multiplication of Legionella pneumophila

N. Bhardwaj, T. W. Nash, M. A. Horwitz

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

We have examined the interaction between interferon-γ (IFN-γ)-activated human monocytes and Legionella pneumophila, the agent of Legionnaires' disease. Human monocytes activated with human recombinant IFN-γ inhibit the intracellular multiplication of L. pneumophila. The degree of inhibition is proportional to the concentration of IFN-γ, and maximal inhibition consistently occurs with ≥ 2 μg/ml. Monoclonal anti-IFN-γ antibody completely neutralized the capacity of IFN-γ to activate monocytes. Monocytes infected 24 hr after explantation maximally inhibit L. pneumophila multiplication if treated with IFN-γ before infection or up to 2 hr after infection; treatment 6 hr or more after infection results in submaximal inhibition. Monocytes infected 48 hr after explantation inhibit L. pneumophila multiplication maximally if treated with IFN-γ up to 12 hr before infection, but submaximally if treated at the time of infection. Once activated, monocytes inhibit L. pneumophila multiplication in the absence of IFN-γ in the culture. Strikingly, monocytes maximally inhibit L. pneumophila multiplication after treatment with IFN-γ for as briefly as 1 hr before infection. In the absence of anti-L. pneumophila antibody, neither IFN-γ-activated monocytes nor nonactivated monocytes kill L. pneumophila. In the presence of specific antibody and complement, IFN-γ-activated monocytes kill a proportion (0.5 log) of an inoculum but not more than nonactivated monocytes. L. pneumophila forms a specialized phagosome in IFN-γ-activated monocytes that does not differ ultrastructurally from the L. pneumophila phagosome in nonactivated monocytes. These results demonstrate that IFN-γ can activate human monocytes to exert a potent anti-microbial effect against a highly virulent intracellular bacterial pathogen. These findings extend previous observations on interactions between activated mononuclear phagocytes and L. pneumophila, and additionally support the hypothesis that cell-mediated immunity plays a major role in host defense against L. pneumophila.

Original languageEnglish
Pages (from-to)2662-2669
Number of pages8
JournalJournal of Immunology
Volume137
Issue number8
StatePublished - 1986
Externally publishedYes

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