Cutting Edge: Resistance to Bacillus anthracis Infection Mediated by a Lethal Toxin Sensitive Allele of Nalp1b/Nlrp1b

Abstract

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.

Noninvasive Imaging Technologies Reveal Edema Toxin as a Key Virulence Factor in Anthrax

“…Possibly, cell death triggered by the toxic effects of LT induces a strong inflammatory reaction, further enhancing neutrophil recruitment, as recently suggested. 35 When both ET and LT toxins were coproduced by the wild-type strain, markedly different patterns of dissemination were observed, depending on the route of infection. In cutaneous infection, the pattern was similar to that of the nontoxinogenic strain, confirming previous reports on the central pathogenic role of the capsule over the toxins in murine cutaneous infections.…”

Carbunco. Prevención de la enfermedad

“…Está demostrado que el FL produce activación del inflamasoma de las células afectadas determinando la activación del sistema de las caspasas y liberación de citoquinas proinflamatorias, originando la muerte rápida de los macrófagos por piroptosis (Muehlbauer et al, 2007;Popov et al, 2002;Terra et al, 2010). Por lo tanto, es posible que mediante este mecanismo puedan haberse eliminado muchas de las células que expresan ANTXR1 en la población de individuos que han estado expuestos previamente y por largo tiempo a la toxina, sobreviviendo aquellas células con baja expresión de receptores.…”

Les inflammasomes

“…Par ailleurs, chez la souris, le facteur létal, un des deux constituants de la toxine létale du bacille de l'anthrax (Bacillus anthracis), est également reconnu par NLRP1 [35]. L'inflammasome a un rôle central dans la lutte contre B. anthracis dans des modèles murins, mais pourrait aussi être responsable des dommages pulmonaires inflammatoires en cas d'inhalation de la toxine létale [36].…”