Cytokine Response to Infection with Bacillus anthracis Spores

Abstract

Bacillus anthracis, the etiological agent of anthrax, is a gram-positive, spore-forming bacterium. The inhalational form of anthrax is the most severe and is associated with rapid progression of the disease and the outcome is frequently fatal. Transfer from the respiratory epithelium to regional lymph nodes appears to be an essential early step in the establishment of infection. This transfer is believed to occur by means of carriage within alveolar macrophages following phagocytosis. Therefore, the ability of B. anthracis to transit through the host macrophage or dendritic cell appears to be an early and critical step in B. anthracis pathogenesis. In this work, we examined the cytokine responses to spore infection in mouse primary peritoneal macrophages, in primary human dendritic cells, and during a spore aerosol infection model utilizing the susceptible A/J mouse strain. We demonstrated that both mouse peritoneal macrophages and human dendritic cells exhibited significant intracellular bactericidal activity during the first hours following uptake, providing the necessary time to mount a cytokine response prior to cell lysis. Strong tumor necrosis factor (TNF-␣) and interleukin-6 (IL-6) responses were seen in mouse peritoneal macrophages. In addition to TNF-␣ and IL-6, human dendritic cells produced the cytokines IL-1␤, IL-8, and IL-12. A mixture of Th1 and Th2 cytokines were detected in sera obtained from infected animals. In this study, we provide further evidence of an acute cytokine response when cells in culture and mice are infected with B. anthracis spores.

Dendritic Cells Endocytose Bacillus anthracis Spores: Implications for Anthrax Pathogenesis

“…Significantly, our study agrees with their MAPK signaling results using a different experimental system, which involved spore infection with permitted outgrowth of B. anthracis bacilli and production of virulence factors. Our study and that of Agrawal et al (34) contrast with a new study (35) that showed no impact of Sterne infection on cytokine secretion. Although our results did not indicate an impact of specific virulence factors on expression of the costimulatory membrane proteins that we examined, Agrawal et al (34) reported a suppression of costimulatory molecule expression with overnight LT preincubation and subsequent LPS stimulation.…”

Bacillus anthracis spores and lethal toxin induce IL‐1β via functionally distinct signaling pathways

“…Previous investigators have added germination-proficient BA spores to macrophage and dendritic cell cultures under conditions that favored germination to bacillary forms and the expression of both LT and anthrolysin O, both of which have been associated with cell death [33][34][35]. This has made it difficult to differentiate between the effects of BA spores and vegetative bacilli on macrophage cytokine responses.…”

Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms

“…Caspase-1 also provides host-protective functions during B. anthracis infection; human DCs and alvelovar macrophages produce IL-1␤ in response to spore infection (48,49). IL-1␤ production in BALB/c mice correlates with early control of bacterial dissemination (50).…”