01904nas a2200301   4500000000100000008004100001260001300042653002200055653002400077653002600101653001800127653002000145653001600165653001100181653001900192653001200211653002500223653001800248100002200266700001500288700001400303700001400317245007900331300001200410490000600422520116000428022001401588       2010                            d  c2010 Nov10aAdaptive Immunity10aAntigens, Bacterial10aComplement Activation10aComplement C310aDendritic Cells10aGlycolipids10aHumans10aInterleukin-1010aleprosy10aMycobacterium leprae10aT-Lymphocytes1 aCallegaro-Filho D1 aShrestha N1 aBurdick A1 aHaslett P00aA potential role for complement in immune evasion by Mycobacterium leprae.  a1373-820 v93 a<p>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.</p>  a1545-9616