ANXA1 down regulates IL-1b

Cutaneous leishmaniasis (CL) is characterized by severe local inflammation, predominantly mediated by IL-1β, TNF, and cytotoxicity, mediators associated with tissue damage and lesion development. Given the high rate of therapeutic failure in Leishmania braziliensis infection, the investigation of molecules that regulate inflammatory response, is an adjuvant therapeutical strategy. Here we investigated the effects of Annexin A1 (ANXA1) on the inflammatory response of CL patients. In silico analyses from our previous transcriptome databases showed 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, IL1B, and IL10 proteins were observed in serum and cultures of skin biopsies in CL patients when compared to HS. The treatment of lesion biopsies with recombinant ANXA1 reduced IL-1β levels without affecting IL-10, indicating a selective anti-inflammatory effect. Additionally, monocyte-derived macrophages from HS produced high levels of ANXA1, IL-1β, and IL-10 upon Leishmania infection. Blockade of FPR2 receptor increased ANXA1 levels. Finally, addition of recombinant ANXA1 to macrophages did not affects 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.