In situ expression of CD40, CD40L (CD154), IL-12, TNF-alpha, IFN-gamma and TGF-beta1 in murine lungs during slowly progressive primary tuberculosis.
The distribution and expression of CD40, its ligand CD40L (154) and related cytokines interleukin-12 (IL-12), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) were studied in the lungs of B6D2F1 hybrid mice during slowly progressive primary tuberculosis (TB) by immunohistochemistry. CD40 and CD40L are implicated in cell-mediated immunity (CMI) causing activation or apoptosis of infected cells. The phenomenon of apoptosis is associated with Mycobacterium tuberculosis survival. In this study, using frozen lung sections (n = 33), our results showed increased CD40, IL-12 and TGF-beta1 expression in macrophages with progression of disease. High percentages of mycobacterial antigens (M.Ags), CD40L and IFN-gamma expression were maintained throughout infection, and TNF-alpha-expressing cells were decreased. In lymphocytes, the percentage of IFN-gamma-positive cells was increased, but CD40L and IL-12 were maintained with the progression of disease. M.Ags, CD40 and CD40L were expressed in the same areas of the lesions. We conclude that changes in the expression of CD40-CD40L and cytokines associated with M. tuberculosis infection favour the hypothesis that M. tuberculosis causes resistance of host cells to apoptosis causing perpetuation of infection.
Mogga
S J
SJ
Centre for International Health, University of Bergen, Bergen, Norway. mogga.josephson@cih.uib.no
Mustafa
T
T
Sviland
L
L
Nilsen
R
R
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D019013:CD40 Antigens; D016207:Cytokines; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma