Identifying a Potential Therapeutic Host Target in Cutaneous Leishmaniasis

Intracellular cutaneous infectious agents can trigger autoreactive immune responses, exacerbating or leading to new acute and chronic systemic illness. Cutaneous leishmaniasis (CL) causes vigorous immunopathologic responses that contribute to mucosal disease and ulceration. In this issue of the Journal of Investigative Dermatology, Novais et al. (2020) expand on their previous work demonstrating that a cytotoxic CD8⁺ response is associated with therapeutic failure. In this study, they show that inhibition of granzyme B with the Jak1/3 inhibitor, tofacitinib, is associated with decreased severity of cutaneous lesions without the attenuation of T helper type 1 signaling or parasite control. Their findings, including the utility of topical delivery, suggest an attractive role for Jak inhibition alongside antiparasitic agents in the treatment of CL in patients.