Anthrax and the inflammasome

Abstract

Anthrax lethal toxin (LT), a major virulence determinant of anthrax disease, induces vascular collapse in mice and rats. LT activates the Nlrp1 inflammasome in macrophages and dendritic cells, resulting in caspase-1 activation, IL-1β and IL-18 maturation and a rapid cell death (pyroptosis). This review presents the current understanding of LT-induced activation of Nlrp1 in cells, and its consequences for toxin-mediated effects in rodent toxin and spore challenge models.

Regulation of Class I Major Histocompatibility Complex (MHC) by Nucleotide-binding Domain, Leucine-rich Repeat-containing (NLR) Proteins

“…1) For the previous studies performed in human cells, it is possible that there are species-specific differences, which are ample among the other NLRs. For example, NLRP1 from humans and mice serve similar functions in inflammasome activation, but the former is responsive to muramyl dipeptide (MDP), whereas the latter is activated by Bacillus anthracis lethal toxin (33). 2) Along this same line, it is possible that there are gene redundancies in mice that are not found in humans.…”

Bacillus anthracis toxins

“…ET causes a wide range of effects at both stages through the generation of cAMP in host cells. While LT does affect infection (in mice and rats) and lethality (only in rats) through its actions on the inflammasome sensor NLRP1 (for detailed review, see [199]), the bulk of LT's effects in both the early and late stages of disease are likely through targeting of the MEK proteins (Figure 13.1).…”

Host immunity to Bacillus anthracis lethal factor and other immunogens: implications for vaccine design

“…The cell biology, pathobiology and vaccinology of anthrax infection have been comprehensively reviewed in recent years [8][9][10][11][12][13]. The purpose of this review is to summarize lessons from some of the recent immunological studies of exposed individuals and animal models, applying this knowledge to appraisal of future vaccine strategies.…”