Mycobacterium tuberculosis Rv2224c modulates innate immune responses

Jyothi Rengarajan, Elissa Murphy, Arnold Park, Cassandra L. Krone, Erik C. Hett, Barry R. Bloom, Laurie H. Glimcher, Eric J. Rubin

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Tuberculosis remains a major global health problem that kills up to 2 million people annually. Central to the success of Mycobacterium tuberculosis (Mtb) as a pathogen is its ability to evade host immunity and to establish a chronic infection. Although its primary intracellular niche is within macrophages, the underlying molecular mechanisms are poorly understood. Here we show that Rv2224c, a cell envelope-associated predicted protease, is critical for Mtb virulence. Disruption of Rv2224c led to prolonged survival of infected mice and highly reduced lung pathology. Absence of Rv2224c enhanced host innate immune responses, compromised the intracellular survival of Mtb in macrophages, and increased its susceptibility to lysozyme. We provide insights into the molecular basis for Rv2224c function by showing that Rv2224c activity promotes processing and extracellular release of the Mtb protein, GroEL2. Inhibition of Rv2224c and its targets offers opportunities for therapeutic interventions and immune-modulatory strategies.

Original languageEnglish
Pages (from-to)264-269
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number1
DOIs
StatePublished - 8 Jan 2008
Externally publishedYes

Keywords

  • Cell envelope
  • Intracellular
  • Macrophages
  • Pathogen

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