Work

Innate Lymphoid Cell 1– and NK Cell–Derived, Early IFNg Release Depends on ICER and Promotes Protection against Leishmania major Infection

Year: 2025

Type: article

Abstract: Innate lymphoid cells (ILCs) participate in different skin diseases. Cutaneous leishmaniasis evokes Th1/Tc1-dominated immunity, while in immune-compromised individuals, a Th2/Treg/Th17-immune response dominates. Only few prior studies investigated the role of ILC in leishmaniasis. We show that following physiologic low dose infection with Leishmania major , both lesional NK cell and ILC1 numbers strongly increase. In addition, early lesional IFNγ production derives from type I ILCs. Genetic ablation of both NK cells and ILC1 (NK/ILC1 Δ mice) led to reduced early IFNγ expression with increased pathology, higher parasite burdens and delayed recovery. Furthermore, expression of inducible cAMP early repressor (ICER) is important for disease outcome, as ICER -/- mice exhibited significantly larger lesions. Interestingly, mice that lack ICER specifically in NK cells and ILC1 phenocopied the worsened disease outcome of ICER -/- mice, while ICER deficiency in T cells or macrophages alone failed to do so. In line, ICER deficiency in NK cells/ILC1 resulted in higher lesional parasite burden with fewer IFNγ-positive ILC1 compared to control animals. Thus, our data shows that both NK cells and ILC1 contribute to early parasite control by releasing IFNγ. ICER expression by ILC1 promotes recruitment of IFNγ + ILC1 in Leishmania infections important for development of protection against this important pathogen.

Source: Journal of Investigative Dermatology

DOI: 10.1016/j.jid.2025.04.027