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IFN‐γ enhances bovine macrophage responsiveness to Mycobacterium bovis : Impact on bacterial replication, cytokine release and macrophage apoptosis
Author(s) -
Denis Michel,
Wedlock D Neil,
Buddle Bryce M
Publication year - 2005
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/j.1440-1711.2005.01386.x
Subject(s) - mycobacterium bovis , macrophage , microbiology and biotechnology , cytokine , tumor necrosis factor alpha , apoptosis , biology , immunology , in vitro , medicine , mycobacterium tuberculosis , tuberculosis , biochemistry , pathology
We sought to determine the impact of bovine IFN‐γ on the interaction between Mycobacterium bovis and bovine macrophages. Bovine macrophages released small amounts of nitric oxide (NO), TNF‐α, IL‐1β and IL‐12 upon infection with bacille Calmette−Guérin (BCG). Prior pulsing of cells with IFN‐γ significantly enhanced the release of NO and IL‐12. Infection of bovine macrophages with virulent M. bovis led to the release of higher levels of pro‐inflammatory mediators, compared to levels released upon BCG infection. IFN‐γ treatment of macrophages enhanced the release of pro‐inflammatory mediators, but did not modify bacterial replication in M. bovis ‐infected macrophages. Treatment of macrophages with a combination of IFN‐γ and LPS led to a reduction in bacterial replication. Infected cells treated with IFN‐γ/LPS progressed mostly through an apoptotic pathway, whereas untreated infected cells eventually died by necrosis. Agents that prevented the acquisition of bacteriostatic activity by activated macrophages also prevented the induction of apoptosis in infected macrophages (IL‐10 and neutralizing anti‐TNF‐α). We conclude that virulent M. bovis is a major determinant of release of pro‐inflammatory cytokines by macrophages. IFN‐γ amplifies the macrophage cytokine release in response to M. bovis . Induction of apoptosis is closely linked to the emergence of macrophage resistance to M. bovis replication, which is dependent on endogenous TNF‐α release.