Compartmentalized bronchoalveolar IFN-gamma and IL-12 response in human pulmonary tuberculosis.
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-gamma-production were observed in CD4(+), CD8(+), gammadeltaTCR(+), and CD56(+) alveolar T cell subpopulations and NK cells (CD3(-)CD56(+)). IFN-gamma-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-12Rbeta1 and IL-12Rbeta2 mRNA in BACs and PBMCs and IFN-gammaR1 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-gamma-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-gamma.
Departamento de Microbiologia, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
Maria Teresa
MT
Herrera
Martha
M
Torres
Denarra
D
Nevels
Carlos Núñez
CN
Perez-Redondo
Jerrold J
JJ
Ellner
Eduardo
E
Sada
Stephan K
SK
Schwander
D000328:Adult; D001431:Bacteriological Techniques; D001980:Bronchi / Q000276:immunology / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000032:analysis; D016906:Interleukin-9 / Q000032:analysis; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D011650:Pulmonary Alveoli / Q000276:immunology / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016212:Transforming Growth Factor beta / Q000032:analysis; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology*
D016906:Interleukin-9; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma