Granuloma formation and host defense in chronic mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1

Erin McElvania Tekippe, Irving C. Allen, Paul D. Hulseberg, Jonathan T. Sullivan, Jessica R. McCann, Matyas Sandor, Miriam Braunstein, Jenny P Y Ting

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

The NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3), its adaptor protein PYCARD (ASC), and caspase-1 during infection with Mycobacterium tuberculosis (Mtb). Mtb infection of macrophages in culture induced IL-1β secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp-/-, Casp- -/-, and WT mice showed no differences in pulmonary IL-1β production, bacterial burden, or long-term survival. In contrast, a significant role was observed for Pycard in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of Pycard-/- mice. Decreased survival of Pycard-/- animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.

Original languageEnglish (US)
Article numbere12320
JournalPloS one
Volume5
Issue number8
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    McElvania Tekippe, E., Allen, I. C., Hulseberg, P. D., Sullivan, J. T., McCann, J. R., Sandor, M., Braunstein, M., & Ting, J. P. Y. (2010). Granuloma formation and host defense in chronic mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1. PloS one, 5(8), [e12320]. https://doi.org/10.1371/journal.pone.0012320