title: Role of gamma interferon and tumor necrosis factor alpha during T-cell-independent and -dependent phases of Mycobacterium avium infection.
abstract: To design an effective immunotherapy for Mycobacterium avium infections, the protective host response to the infection must be known. Here we analyzed the role of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in the innate and acquired responses to M. avium infections in mice. T-cell depletion studies showed that CD4+ T cells were required for control of the infection. CD(4+)-depleted mice showed enhanced bacterial proliferation and at the same time showed a reduction in the level of expression of both IFN-gamma and TNF-alpha mRNAs in spleen cells. In contrast, M. bovis BCG immunization restricted M. avium proliferation and at the same time promoted expression of the mRNAs for the two cytokines. In vivo depletion studies using specific monoclonal antibodies showed that both IFN-gamma and TNF-alpha are involved in an early protection possibly involving NK cells, and furthermore, IFN-gamma is involved in the later T-cell-protective response to infection. In vivo neutralization of IFN-gamma during M. avium infection also blocked the priming for enhanced TNF-alpha secretion triggered by endotoxin. Both cytokines were found to be involved in the resistance expressed in BCG-immunized animals and exhibited additive bacteriostatic effects in vitro on bone marrow-derived macrophages infected with different strains of M. avium. These data suggest that both cytokines act in an additive or synergistic fashion in the induction of bacteriostasis and that IFN-gamma is also involved in priming TNF-alpha secretion.
authors.affiliation: Centro de Citologia Experimental, University of Porto, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Appelberg
authors.forename: A G
authors.initials: AG
authors.lastname: Castro
authors.forename: J
authors.initials: J
authors.lastname: Pedrosa
authors.forename: R A
authors.initials: RA
authors.lastname: Silva
authors.forename: I M
authors.initials: IM
authors.lastname: Orme
authors.forename: P
authors.initials: P
authors.lastname: Minóprio
mesh_terms: D000818:Animals; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009162:Mycobacterium avium / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma