Bacillus anthracis lethal toxin negatively modulates ILC3 function through perturbation of IL-23-mediated MAPK signaling

Bacillus anthracis,the causative agent of anthrax,secretes lethal toxin that down-regulates immune functions. translocation of b. anthracis across mucosal epithelia is key for its dissemination and pathogenesis. group 3 innate lymphocytes (ilc3s) are important in mucosal barrier maintenance due to their expression of the cytokine il-22,a critical regulator of tissue responses and repair during homeostasis and inflammation. we found that b. anthracis lethal toxin perturbed ilc3 function in vitro and in vivo,revealing an unknown il-23-mediated mapk signaling pathway. lethal toxin had no effects on the canonical stat3-mediated il-23 signaling pathway. rather lethal toxin triggered the loss of several map2k kinases,which correlated with reduced activation of downstream erk1/2 and p38,respectively. inhibition studies showed the importance of mapk signaling in il-23-mediated production of il-22. our finding that mapk signaling is required for optimal il-22 production in ilc3s may lead to new approaches for targeting il-22 biology. © 2017 seshadri et al.