Annexin A1 Is Involved in the Resolution of Inflammatory Responses during Leishmania braziliensis Infection [INFECTIOUS DISEASE AND HOST RESPONSE]

Leishmaniases are diseases caused by several Leishmania species. Leishmania (Viannia) braziliensis can cause localized cutaneous leishmaniasis (LCL), which heals spontaneously, or mucosal leishmaniasis (ML), characterized by chronic and intense inflammation and scanty parasitism. Annexin A1 (AnxA1) is a protein involved in modulation and resolution of inflammation through multiple mechanisms. In the present study, the role of AnxA1 was investigated in L. braziliensis–infected BALB/c mice. AnxA1 levels increased at the peak of tissue lesion and parasitism in infected mice. AnxA1 increased also after L. braziliensis infection of BALB/c (wild-type [WT]) bone marrow derived macrophages. Despite a lower parasite intake, parasite burden in bone marrow-derived macrophages from AnxA1^–/– mice was similar to WT and associated with an early increase of TNF-α and, later, of IL-10. AnxA1^–/– mice controlled tissue parasitism similarly to WT animals, but they developed significantly larger lesions at later stages of infection, with a more pronounced inflammatory infiltrate and increased specific production of IFN-, IL-4, and IL-10. AnxA1^–/– mice also presented higher phosphorylation levels of ERK-1/2 and p65/RelA (NF-B) and inducible NO synthase expression, suggesting that AnxA1 may be involved in modulation of inflammation in this model of experimental leishmaniasis. Finally, assessment of AnxA1 levels in sera from patients with LCL or ML revealed that ML patients had higher levels of serum AnxA1 than did LCL patients or control subjects. Collectively, these data indicate that AnxA1 is actively expressed during L. braziliensis infection. In the absence of AnxA1, mice are fully able to control parasite replication, but they present more intense inflammatory responses and delayed ability to resolve their lesion size.

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