FcRγIIA attenuates pathology of cutaneous leishmaniasis and modulates ITAMa/i balance.

Autor: Hammi I; Health & Environment Laboratory, Ain Chock Faculty of Sciences, Hassan II University of Casablanca (UH2C), Casablanca, Morocco.; INSERM UMR-S-MD 1197, Ministère des Armées et Université Paris Saclay, Villejuif, France., Giron-Michel J; INSERM UMR-S-MD 1197, Ministère des Armées et Université Paris Saclay, Villejuif, France., Riyad M; Laboratory of Cellular and Molecular Pathology, Faculty of Medicine and Pharmacy, UH2C, Casablanca, Morocco., Akarid K; Health & Environment Laboratory, Ain Chock Faculty of Sciences, Hassan II University of Casablanca (UH2C), Casablanca, Morocco., Arnoult D; INSERM UMR-S-MD 1197, Ministère des Armées et Université Paris Saclay, Villejuif, France. damien.arnoult@inserm.fr.
Jazyk: angličtina
Zdroj: Parasites & vectors [Parasit Vectors] 2024 Dec 18; Vol. 17 (1), pp. 517. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1186/s13071-024-06593-y
Abstrakt: Background: Leishmania is the causal parasite of leishmaniasis, a neglected tropical disease affecting millions of individuals worldwide, and its dissemination is linked to climate change. Despite the complexity and effectiveness of the immune response, the parasite has developed many strategies to evade it and take control of the host cell to replicate. These evasion strategies start at early stages of infection by hijacking immune receptors to mitigate the cellular response. In this study, we examined whether Leishmania uses the Fc receptor FcγRIIA/CD32a and its downstream signaling pathways to evade the host immune response.
Methods: Regarding in vivo studies, CD32a transgenic mice and the corresponding wild types were infected with Leishmania major Friedlin strain. For the in vitro experiments, BMDMs isolated from WT or CD32a transgenic mice and control or CD32a knockdown differentiated THP-1s were infected with two species of Leishmania, Leishmania major and L. tropica.
Results: In vivo, expression of FcγRIIA/CD32a was found to accelerate the signs of inflammation while simultaneously preventing the formation of necrotic lesions after Leishmania infection. In infected macrophages, the presence of FcγRIIA/CD32a did not affect the secretion of proinflammatory cytokines, while the balance between ITAMa and ITAMi proteins was disturbed with improved Fyn and Lyn activation. Unexpectedly, infection with L. tropica but not L. major triggered an intracytoplasmic processing of FcγRIIA/CD32a.
Conclusions: Our observations underscore the significance of FcγRIIA/CD32a in cutaneous leishmaniasis and its potential use as a therapeutic target.
Competing Interests: Declarations. Consent for publication: All the authors agree and consent for publication of the results presented in this manuscript. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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