TY - JOUR
T1 - Granuloma formation and host defense in chronic mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1
AU - McElvania Tekippe, Erin
AU - Allen, Irving C.
AU - Hulseberg, Paul D.
AU - Sullivan, Jonathan T.
AU - McCann, Jessica R.
AU - Sandor, Matyas
AU - Braunstein, Miriam
AU - Ting, Jenny P Y
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0012320
DO - 10.1371/journal.pone.0012320
M3 - Article
C2 - 20808838
AN - SCOPUS:77957908944
SN - 1932-6203
VL - 5
JO - PloS one
JF - PloS one
IS - 8
M1 - e12320
ER -