TY - JOUR
T1 - Cutting edge
T2 - Caspase-1 independent IL-1β production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo
AU - Mayer-Barber, Katrin D.
AU - Barber, Daniel L.
AU - Shenderov, Kevin
AU - White, Sandra D.
AU - Wilson, Mark S.
AU - Cheever, Allen
AU - Kugler, David
AU - Hieny, Sara
AU - Caspar, Patricia
AU - Núñez, Gabriel
AU - Schlueter, Dirk
AU - Flavell, Richard A.
AU - Sutterwala, Fayyaz S.
AU - Sher, Alan
PY - 2010/4/1
Y1 - 2010/4/1
N2 - To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1β-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1β signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1β expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1β maturation, showed unimpaired IL-1β production and importantly, were considerably less susceptible to infection than IL-1β deficient mice. Together our findings reveal a major role for IL-1β in host resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
AB - To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1β-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1β signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1β expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1β maturation, showed unimpaired IL-1β production and importantly, were considerably less susceptible to infection than IL-1β deficient mice. Together our findings reveal a major role for IL-1β in host resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
UR - http://www.scopus.com/inward/record.url?scp=77951628300&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951628300&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0904189
DO - 10.4049/jimmunol.0904189
M3 - Article
C2 - 20200276
AN - SCOPUS:77951628300
SN - 0022-1767
VL - 184
SP - 3326
EP - 3330
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -