A potential role for complement in immune evasion by Mycobacterium leprae

Donato Callegaro-Filho, Niraj Shrestha, Anne E. Burdick, Patrick A.J. Haslett

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1373-1382
Number of pages10
JournalJournal of Drugs in Dermatology
Volume9
Issue number11
StatePublished - Nov 1 2010

ASJC Scopus subject areas

  • Dermatology

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