Cutting edge: resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of Nalp1b/Nlrp1b.
Pathogenesis of Bacillus anthracis is associated with the production of lethal toxin (LT), which activates the murine Nalp1b/Nlrp1b inflammasome and induces caspase-1-dependent pyroptotic death in macrophages and dendritic cells. In this study, we investigated the effect of allelic variation of Nlrp1b on the outcome of LT challenge and infection by B. anthracis spores. Nlrp1b allelic variation did not alter the kinetics or pathology of end-stage disease induced by purified LT, suggesting that, in contrast to previous reports, macrophage lysis does not contribute directly to LT-mediated pathology. However, animals expressing a LT-sensitive allele of Nlrp1b showed an early inflammatory response to LT and increased resistance to infection by B. anthracis. Data presented here support a model whereby LT-mediated activation of Nlrp1b and subsequent lysis of macrophages is not a mechanism used by B. anthracis to promote virulence, but rather a protective host-mediated innate immune response.
Terra
Jill K
JK
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cote
Christopher K
CK
France
Bryan
B
Jenkins
Amy L
AL
Bozue
Joel A
JA
Welkos
Susan L
SL
LeVine
Steven M
SM
Bradley
Kenneth A
KA
D000818:Animals; D000881:Anthrax / Q000235:genetics* / Q000276:immunology*; D000942:Antigens, Bacterial / Q000633:toxicity; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001408:Bacillus anthracis / Q000276:immunology / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000633:toxicity; D020022:Genetic Predisposition to Disease; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D000942:Antigens, Bacterial; D051017:Apoptosis Regulatory Proteins; D001427:Bacterial Toxins; C509168:Nalp1b protein, mouse; C030325:anthrax toxin