Annexin A1 downregulates in vitro IL-1β production in L. braziliensis-infected cells

Cutaneous leishmaniasis (CL) is an infectious disease characterized by severe local inflammatory response, predominantly mediated by cytokines such as IL-1<i>β</i> and TNF, and cytotoxicity, contributing to tissue damage and lesion development. Given the high rate of therapeutic failure in <i>Leishmania braziliensis</i> 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 <i>in silico</i> analyses from our previous transcriptome databases and found increased expression of <i>ANXA1, IL1B</i>, and <i>IL10</i> genes in skin biopsies from CL patients when compared to healthy skin from healthy subjects (HS). Also, increased levels of ANXA1, IL1<i>β</i>, 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-1<i>β</i> levels without affecting IL-10 secretion, indicating a selective anti-inflammatory effect. Additionally, monocyte-derived macrophages from HS increased ANXA1, IL-1<i>β</i>, and IL-10 production upon <i>Leishmania</i> 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 <i>Leishmania</i>. Our findings demonstrate that ANXA1 negatively regulates IL-1<i>β</i> 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.