Your new experience awaits. Try the new design now and help us make it even better

ORIGINAL RESEARCH article

Front. Immunol.

Sec. Microbial Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1685264

This article is part of the Research TopicImmunology of Vector-borne Tropical Diseases of the AmericasView all 5 articles

Annexin A1 Downregulates in vitro IL-1β Production in L. braziliensis-infected cells

Provisionally accepted
  • Gonçalo Moniz Institute (IGM), Salvador, Brazil

The final, formatted version of the article will be published soon.

Cutaneous leishmaniasis (CL) is an infectious disease characterized by severe local inflammatory response, predominantly mediated by cytokines such as IL-1β and TNF, and cytotoxicity, contributing to tissue damage and lesion development. Given the high rate of therapeutic failure in Leishmania braziliensis transmission areas, the investigation of molecules that regulate inflammatory response has become a promising adjuvant therapeutical strategy. In this study we investigated the effects of Annexin A1 (ANXA1) on the inflammatory response of CL patients. We initially performed in silico analyses from our previous transcriptome databases and found increased expression of ANXA1, IL1B, and IL10 genes in skin biopsies from CL patients when compared to healthy skin from healthy subjects (HS). Also, increased levels of ANXA1, IL-1β, and IL10 proteins were observed in serum levels and cultures of skin biopsies in CL patients when compared to HS. Treatment of lesion biopsies with recombinant ANXA1 reduced IL-1β levels without affecting IL-10 secretion, indicating a selective anti-inflammatory effect. Additionally, monocyte-derived macrophages from HS increased ANXA1, IL-1β, and IL-10 production upon Leishmania infection. Blockade of FPR2 receptor increased ANXA1 levels. Finally, addition of recombinant ANXA1 to macrophages did not affect the ability of these cells to kill Leishmania. Our findings demonstrate that ANXA1 negatively regulates IL-1β in CL, without impairing anti-inflammatory mechanisms or macrophage microbicidal activity, highlighting its potential use as an adjuvant therapy for controlling inflammation and disease progression.

Keywords: Annexin A1, cutaneous leishmaniasis, L. braziliensis, immune response, Inflammation

Received: 13 Aug 2025; Accepted: 06 Oct 2025.

Copyright: © 2025 Santos, Nascimento, Santana, Carvalho and Carvalho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Lucas P. Carvalho, carvalholp76@gmail.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.