Journal article
Dual role for inflammasome sensors NLRP1 and NLRP3 in murine resistance to Toxoplasma gondii
G Gorfu, KM Cirelli, MB Melo, K Mayer-Barber, D Crown, BH Koller, S Masters, A Sher, SH Leppla, M Moayeri, JPJ Saeij, ME Grigg
Mbio | Published : 2014
Open access
Abstract
Induction of immunity that limits Toxoplasma gondii infection in mice is critically dependent on the activation of the innate immune response. In this study, we investigated the role of cytoplasmic nucleotide-binding domain and leucine-rich repeat containing a pyrin domain (NLRP) inflammasome sensors during acute toxoplasmosis in mice. We show that in vitro Toxoplasma infection of murine bone marrow-derived macrophages activates the NLRP3 inflammasome, resulting in the rapid production and cleavage of interleukin-1β (IL-1β), with no measurable cleavage of IL-18 and no pyroptosis. Paradoxically, Toxoplasma-infected mice produced large quantities of IL-18 but had no measurable IL-1β in their s..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This work was supported in part by the Intramural Research Program of the NIH and NIAID (M. E. G., S. H. L., and A. S.). G. G. was supported by a research fellowship award from the Crohn's & Colitis Foundation of America (CCFA) and is a CCFA Helmsley Scholar. K. M. C. was supported by NIH grant AI104170. J.P.J.S. was supported by R01-AI080621 and a Pew Scholar in the Biomedical Sciences Award. M. E. G. is a scholar of the Canadian Institute for Advanced Research (CIFAR) Program for Integrated Microbial Biodiversity.