Inflammasome Sensor NLRP1 Controls Rat Macrophage Susceptibility to Toxoplasma gondii

• DOI: 10.1371/journal.ppat.1003927
• Publication Date: 2014-03-13T21:05:05Z
• Authors: Kimberly M. Cirelli; Gezahegn Gorfu; Musa A. Hassan; Morton Printz; Devorah Crown; Stephen H. Leppla; Michael E. Grigg; Jeroen P. J. Saeij; Mahtab Moayeri
• Keywords: Pyroptosis; NLRP1; Intracellular parasite

Toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. Rats vary in their susceptibility to this parasite. The Toxo1 locus conferring resistance rats was previously mapped region chromosome 10 containing Nlrp1. This gene encodes inflammasome sensor controlling macrophage sensitivity anthrax lethal toxin (LT) induced rapid cell death (pyroptosis). We show here rat strain differences infected pyroptosis, IL-1β/IL-18 processing, and inhibition proliferation are perfectly correlated with NLRP1 sequence, while inversely LT-induced death. Using recombinant inbred rats, SNP analyses whole transcriptome expression studies, we narrowed the candidate genes for control Toxoplasma-mediated pyroptosis four genes, one which Knockdown Nlrp1 pyroptosis-sensitive macrophages resulted higher replication protection from Reciprocally, overexpression variant Toxoplasma-sensitive pyroptosis-resistant cells led sensitization these resistant macrophages. Our findings reveal as novel activator