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T‐cell‐independent granuloma formation in response to Mycobacterium avium : role of tumour necrosis factor‐α and interferon‐γ
Author(s) -
SMITH D.,
HÄNSCH H.,
BANCROFT G.,
EHLERS S.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00384.x
Subject(s) - biology , tumor necrosis factor alpha , cytokine , macrophage , interferon , immunology , chemokine , granuloma , phagocyte , interferon gamma , interleukin 10 , microbiology and biotechnology , immune system , in vitro , biochemistry
SUMMARY We used Mycobacterium avium infection in severe combined immunodeficiency (SCID) mice to examine T‐cell‐independent mechanisms of inflammatory cell recruitment. SCID mice infected with a virulent strain of M. avium (TMC724) were able to recruit macrophages to sites of mycobacterial replication and formed organized and coherent granulomas in the absence of functional T cells. Phagocyte recruitment was almost totally ablated by neutralization of either tumour necrosis factor‐α (TNF‐α) or interferon‐γ (IFN‐γ) in vivo demonstrating that granuloma formation was dependent on the presence of these cytokines. This was concomitant with a reduction in the in situ cytokine mRNA levels otherwise induced in infected mice, for chemokines, pro‐inflammatory and regulatory cytokines, including TNF‐α, IFN‐γ, macrophage inflammatory protein‐1α, interleukin‐1β (IL‐1β) and IL‐10. Furthermore, in vivo treatment of infected mice with anti‐asialo GM‐1 antisera, which depletes natural killer (NK) cells, prevented recruitment of inflammatory cells. In vitro studies confirmed that M. avium was able to elicit IFN‐γ from SCID spleen in a dose‐dependent manner. These data show for the first time that secretion of IFN‐γ from NK cells can mediate a T‐cell‐independent pathway of granuloma formation and cellular infiltration in response to mycobacteria.