Mycobacterium leprae inhibits dendritic cell activation and maturation.
Leprosy presents with a clinical spectrum of skin lesions that span from strong Th1-mediated cellular immunity and control of bacillary growth at one pole to poor Ag-specific T cell immunity with extensive bacillary load and Th2 cytokine-expressing lesions at the other. To understand how the immune response to Mycobacterium leprae is regulated, human dendritic cells (DC), potent inducers of adaptive immune responses, exposed to M. leprae, Mycobacterium tuberculosis (Mtb), and Mycobacterium bovis bacillus Calmette-Guerin (BCG) were studied for their ability to be activated and to prime T cell proliferation. In contrast with Mtb and BCG, M. leprae did not induce DC activation/maturation as measured by the expression of selected surface markers and proinflammatory cytokine production. In MLR, T cells did not proliferate in response to M. leprae-stimulated DC. Interestingly, M. leprae-exposed MLR cells secreted increased Th2 cytokines as well as similar Th1 cytokine levels as compared with Mtb- and BCG-exposed cells. Gene expression analysis revealed a reduction in levels of mRNA of DC activation and maturation markers following exposure to M. leprae. Our data suggest that M. leprae does not induce and probably suppresses in vitro DC maturation/activation, whereas Mtb and BCG are stimulatory.
Murray
Rose Ann
RA
Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute, Newark, NJ 07103, USA.
Siddiqui
Mahveen Ruby
MR
Mendillo
Megan
M
Krahenbuhl
James
J
Kaplan
Gilla
G
D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D015870:Gene Expression; D006801:Humans; D009000:Monocytes / Q000187:drug effects; D009163:Mycobacterium bovis / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics; D010587:Phagocytosis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
D015703:Antigens, CD; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger