Group 3 innate lymphocytes (ILC3s) are important immune cells within mucosal tissues and protect against
bacterial infections. They can be activated in response to the innate
cytokines IL-23 or IL-1β, which rapidly increases their production of effector molecules that regulate barrier functions. Pathogens can subvert these anti-bacterial effects to evade mucosal defenses to infect the host. Bacillus anthracis, the causative agent of
anthrax, produces two major toxins that can modulate the immune response. We have previously shown that lethal toxin downmodulates the function of ILC3s. On the other hand,
edema toxin has been shown promote T helper 17 (Th17) cell differentiation, adaptive counterparts of ILC3s, via elevation of cyclic
adenosine monophosphate (cAMP). We hypothesized that
edema toxin may also modulate ILC3 function. In this study, we show that
edema toxin has the opposite effect of lethal toxin;
edema toxin directly activates ILC3s independently of innate
cytokine stimulation. Treatment of a mouse ILC3-like cell line with
edema toxin, a potent
adenylate cyclase, upregulated production of the
cytokine IL-22, a major effector molecule of ILC3s and a critical factor in maintaining mucosal barriers.
Forskolin treatment phenocopied the effect observed with
edema toxin and led to an increase in CREB phosphorylation in ILC3s. This observation has potential implications for a role for cAMP signaling in the activation of ILC3s.