Artigo
A Potential Role for Complement in Immune Evasion by Mycobacterium leprae
Fecha
2010-11-01Registro en:
Journal Of Drugs In Dermatology. New York: Journal Of Drugs In Dermatology, v. 9, n. 11, p. 1373-1382, 2010.
1545-9616
WOS:000283701200008
Autor
Callegaro-Filho, Donato [UNIFESP]
Shrestha, Niraj
Burdick, Anne E.
Haslett, Patrick A. J.
Institución
Resumen
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 naive 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.