A potential role for complement in immune evasion by Mycobacterium leprae.
Lepromatous leprosy is a model of immune evasion wherein pathogen-specific IL-10-secreting T cells and concomitant failure of Th-1 immunity permit uncontrolled proliferation of the intracellular pathogen, Mycobacterium leprae (M. leprae). The mechanism of this immune escape is unknown. Here, the authors report that phenolic glycolipid-1 (PGL-1), a major and distinguishing feature of the M. leprae cell wall, is expressed in the cell membrane of M. leprae-infected human dendritic cells, where it can activate complement in human serum. The authors demonstrate that PGL-1 and the C3 component of complement colocalize in lipid rafts in the dendritic cell membrane, and enter the immune synapse upon co-culture of M. leprae-infected DCs and T cells. Hence, activated C3 is strategically located to costimulate naïve T cells via the complement regulatory protein, CD46, a process known to stimulate the differentiation of IL-10-secreting regulatory T cells. These observations suggest a potential novel mechanism of immune evasion, wherein M. leprae may subvert host natural immunity to provoke an adaptive response that favors bacillary survival.
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Donato
D
Callegaro-Filho
Niraj
N
Shrestha
Anne E
AE
Burdick
Patrick A J
PA
Haslett
D056704:Adaptive Immunity; D000942:Antigens, Bacterial / Q000378:metabolism; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007918:Leprosy / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D003176:Complement C3; D006017:Glycolipids; C045169:phenolic glycolipid I, Mycobacterium leprae; D016753:Interleukin-10