TY - JOUR
T1 - Compartmentalized bronchoalveolar IFN-γ and IL-12 response in human pulmonary tuberculosis
AU - Herrera, Maria Teresa
AU - Torres, Martha
AU - Nevels, Denarra
AU - Perez-Redondo, Carlos Núñez
AU - Ellner, Jerrold J.
AU - Sada, Eduardo
AU - Schwander, Stephan K.
PY - 2009/1
Y1 - 2009/1
N2 - Human tuberculosis (TB) principally involves the lungs, where local immunity impacts on the load of Mycobacterium tuberculosis (M.tb). Because concomitants of local Th1 immunity are still under-explored in humans, we characterized immune responses in bronchoalveolar cells (BACs) and systemically in peripheral blood mononuclear cells (PBMCs) in persons with active pulmonary TB and in healthy community controls. PPD- and live M.tb-induced IFN-γ-production were observed in CD4+, CD8+, γδTCR+, and CD56+ alveolar T cell subpopulations and NK cells (CD3-CD56+). IFN-γ-producing CD4+ T cells (mostly CD45RO+) were more abundant (p <0.05). M.tb-induced IL-12p70, but interestingly also IL-4, was increased (p <0.05) in BACs from TB patients. Constitutive expression of IL-12Rβ1 and IL-12Rβ2 mRNA in BACs and PBMCs and IFN-γR1 in BACs was similar in both study groups. Data were normalized to account for differences in proportions of alveolar T cells and macrophages in the study groups. IFN-γ-production and its induction by IL-12R engagement occur virtually unimpaired in the bronchoalveolar spaces of patients with pulmonary TB. The reasons for the apparent failure to control M. tuberculosis growth during active pulmonary TB disease is unknown but could be the expression of locally acting immunosuppressive mechanisms that subvert the antimycobacterial effects of IFN-γ.
AB - Human tuberculosis (TB) principally involves the lungs, where local immunity impacts on the load of Mycobacterium tuberculosis (M.tb). Because concomitants of local Th1 immunity are still under-explored in humans, we characterized immune responses in bronchoalveolar cells (BACs) and systemically in peripheral blood mononuclear cells (PBMCs) in persons with active pulmonary TB and in healthy community controls. PPD- and live M.tb-induced IFN-γ-production were observed in CD4+, CD8+, γδTCR+, and CD56+ alveolar T cell subpopulations and NK cells (CD3-CD56+). IFN-γ-producing CD4+ T cells (mostly CD45RO+) were more abundant (p <0.05). M.tb-induced IL-12p70, but interestingly also IL-4, was increased (p <0.05) in BACs from TB patients. Constitutive expression of IL-12Rβ1 and IL-12Rβ2 mRNA in BACs and PBMCs and IFN-γR1 in BACs was similar in both study groups. Data were normalized to account for differences in proportions of alveolar T cells and macrophages in the study groups. IFN-γ-production and its induction by IL-12R engagement occur virtually unimpaired in the bronchoalveolar spaces of patients with pulmonary TB. The reasons for the apparent failure to control M. tuberculosis growth during active pulmonary TB disease is unknown but could be the expression of locally acting immunosuppressive mechanisms that subvert the antimycobacterial effects of IFN-γ.
KW - BAL cells
KW - Compartmentalization
KW - Human pulmonary tuberculosis
KW - Interferon gamma
KW - Interleukin 10
KW - Interleukin 12
KW - Interleukin 4
KW - Mycobacterium tuberculosis
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U2 - 10.1016/j.tube.2008.08.002
DO - 10.1016/j.tube.2008.08.002
M3 - Article
C2 - 18848499
AN - SCOPUS:58149116814
VL - 89
SP - 38
EP - 47
JO - Bulletin of the International Union Against Tuberculosis and Lung Disease
JF - Bulletin of the International Union Against Tuberculosis and Lung Disease
SN - 1472-9792
IS - 1
ER -