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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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

Fingerprint

Autophagy
Antigen Presentation
Mycobacterium tuberculosis
Histocompatibility Antigens Class II
Major Histocompatibility Complex
Genetic Loci
Adaptive Immunity
Mycobacterium
Phagocytes
Infection
Innate Immunity
Dendritic Cells
Immunity
Vaccination
Proteins
Genome
Growth
Genes

ASJC Scopus subject areas

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

Cite this

Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE-PGRS47. / Saini, Neeraj K.; Baena, Andres; Ng, Tony W.; Venkataswamy, Manjunatha M.; Kennedy, Steven C.; Kunnath-Velayudhan, Shajo; Carreño, Leandro J.; Xu, Jiayong; Chan, John; Larsen, Michelle H.; Jacobs, William R.; Porcelli, Steven A.

In: Nature Microbiology, Vol. 1, 16133, 15.08.2016.

Research output: Contribution to journalArticle

Saini, Neeraj K. ; Baena, Andres ; Ng, Tony W. ; Venkataswamy, Manjunatha M. ; Kennedy, Steven C. ; Kunnath-Velayudhan, Shajo ; Carreño, Leandro J. ; Xu, Jiayong ; Chan, John ; Larsen, Michelle H. ; Jacobs, William R. ; Porcelli, Steven A. / Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE-PGRS47. In: Nature Microbiology. 2016 ; Vol. 1.
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