Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE-PGRS47

Neeraj K. Saini, Andres Baena, Tony W. Ng, Manjunatha M. Venkataswamy, Steven C. Kennedy, Shajo Kunnath-Velayudhan, Leandro J. Carreño, Jiayong Xu, John Chan, Michelle H. Larsen, William R. Jacobs, Steven A. Porcelli

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Abstract

Suppression of major histocompatibility complex (MHC) class II antigen presentation is believed to be among the major mechanisms used by Mycobacterium tuberculosis to escape protective host immune responses. Through a genome-wide screen for the genetic loci of M. tuberculosis that inhibit MHC class II-restricted antigen presentation by mycobacteria-infected dendritic cells, we identified the PE-PGRS47 protein as one of the responsible factors. Targeted disruption of the PE-PGRS47 (Rv2741) gene led to attenuated growth of M. tuberculosis in vitro and in vivo, and a PE-PGRS47 mutant showed enhanced MHC class II-restricted antigen presentation during in vivo infection of mice. Analysis of the effects of deletion or over-expression of PE-PGRS47 implicated this protein in the inhibition of autophagy in infected host phagocytes. Our findings identify PE-PGRS47 as a functionally relevant, non-redundant bacterial factor in the modulation of innate and adaptive immunity by M. tuberculosis, suggesting strategies for improving antigen presentation and the generation of protective immunity during vaccination or infection.

Original languageEnglish (US)
Article number16133
JournalNature Microbiology
Volume1
DOIs
StatePublished - Aug 15 2016

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ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology
  • Immunology
  • Microbiology (medical)
  • Cell Biology
  • Genetics

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