Phosphatidylserine Blockade Limits Systemic Dissemination of Leishmania Amazonensis Amastigotes

Abstract

Leishmania amazonensis is associated with cases of cutaneous, disseminated, diffuse, mucosal, and visceral leishmaniasis (VL). The mechanisms underlying its ability to persist and spread after the initial clinical cure are unclear, although intrinsic characteristics of the parasite and the host may be involved. Phosphatidylserine (PS) is a pathogenic factor in both experimental models and in patients. It is related to macrophage infection, regulation of inflammatory and immune responses, and the extent and severity of the clinical outcomes of the disease. In a murine model of systemic infection, treatment with PS‐targeting antagonist antibodies significantly reduced parasite burden in the spleen. In parallel, the number and size of disseminated skin lesions were consistently reduced. These effects correlated with a substantial decrease in interleukin‐10 (IL‐10) and transforming growth factor‐β (TGF‐β) production by splenocytes stimulated with leishmanial antigens, indicating a reversal of the regulatory immune profile commonly associated with chronic infection. These findings support a critical role for PS in the dissemination and visceralization of Leishmania amazonensis, highlighting its contribution to immune evasion and the pathogenesis of severe disease forms.