IFN-gamma and NO in mycobacterial disease: new jobs for old hands.
Granulomatous disease following exposure to Mycobacterium tuberculosis, Mycobacterium leprae or Mycobacterium avium is correlated with strong inflammatory and protective responses. The mouse model of mycobacterial infection provides an excellent tool with which to examine the inter-relationship between protective cell-mediated immunity and tissue-damaging hypersensitivity. It is well established that T cells and interferon (IFN)-gamma are necessary components of anti-bacterial protection. We propose that IFN-gamma also modulates the local cellular response by downregulating lymphocyte activation and by driving T cells into apoptosis, and that the events that limit excessive inflammation are largely mediated by IFN-gamma-induced nitric oxide (NO). In several murine models of mycobacterial infection, the absence of IFN-gamma and/or NO results in dysregulated granuloma formation and increased lymphocytic responses, which, in the case of M. avium infection, even leads to reduced bacterial growth.
Cooper
Andrea M
AM
The Trudeau Institute, PO Box 59, 100 Algonquin Ave, Saranac Lake, NY 12983, USA. acooper@trudeauinstitute.org
Adams
Linda B
LB
Dalton
Dyana K
DK
Appelberg
Rui
R
Ehlers
Stefan
S
D000818:Animals; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism*; D007918:Leprosy / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D009164:Mycobacterium Infections / Q000276:immunology*; D009162:Mycobacterium avium; D009163:Mycobacterium bovis; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000473:pathology
D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase