Annexin A1 improves immune responses and control of tissue parasitism during Leishmania amazonensis infection in BALB/c mice

• Published in: Biomedicine & pharmacotherapy 2024-03, Vol.172, p.116254-116254, Article 116254
• Main Authors: Ricotta, Tiago Queiroga Nery, dos Santos, Liliane Martins, Oliveira, Leandro Gonzaga, Souza-Testasicca, Míriam C., Nascimento, Frederico Crepaldi, Vago, Juliana P., Carvalho, Antônio Felipe S., Queiroz-Junior, Celso Martins, Sousa, Lirlândia P., Fernandes, Ana Paula
• Format: Article
• Language: English
• Subjects: Annexin A1; Inflammation; Leishmania amazonensis; Leishmaniasis; Treatment
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2024.116254

Leishmaniases, a group of diseases caused by the species of the protozoan parasite Leishmania, remains a significant public health concern worldwide. Host immune responses play a crucial role in the outcome of Leishmania infections, and several mediators that regulate inflammatory responses are potential targets for therapeutic approaches. Annexin A1 (AnxA1), an endogenous protein endowed with anti-inflammatory and pro-resolving properties, has emerged as a potential player. We have shown that during L. braziliensis infection, deficiency of AnxA1 exacerbates inflammatory responses but does not affect parasite burden. Here, we have investigated the role of AnxA1 in L. amazonensis infection, given the non-healing and progressive lesions characteristic of this infectious model. Infection of AnxA1 KO BALB/c mice resulted in increased lesion size and tissue damage associated with higher parasite burdens and enhanced inflammatory response. Notably, therapeutic application of the AnxA1 peptidomimetic Ac2–26 improves control of parasite replication and increases IL-10 production in vivo and in vitro, in both WT and AnxA1 KO mice. Conversely, administration of WRW4, an inhibitor of FPR2/3, resulted in larger lesions and decreased production of IL-10, suggesting that the effects of AnxA1 during L. amazonensis infection are associated with the engagement of these receptors. Our study illuminates the role of AnxA1 in L. amazonensis infection, demonstrating its impact on the susceptibility phenotype of BALB/c mice. Furthermore, our results indicate that targeting the AnxA1 pathway by using the Ac2–26 peptide could represent a promising alternative for new treatments for leishmaniasis. [Display omitted] •The role of the mediator AnxA1 in Leishmania infection is not yet understood.•Lack of endogenous AnxA1 increases susceptibility of BALB/c mice to Leishmania amazonensis infection.•Treatment with the peptide Ac2- 26 reduces lesion progression, induces IL-10 production and improves parasite clearance.•Inhibition of the AnxA1 receptor FPR2 results in larger lesions in infected BALB/c mice.•Ac2-26 is a potential target for immunotherapy treatment in Leishmania infection.