TREM-1 Expression on the Surface of Neutrophils in Patients With Visceral Leishmaniasis Is Associated With Immunopathogenesis

Abstract

Visceral leishmaniasis (VL) is a systemic chronic and potentially fatal disease for humans. Mechanisms related to the dysregulation of the inflammatory response may be involved in both the pathogenesis and prognosis of VL. Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) is a receptor constitutively expressed on neutrophils and monocyte subsets. The protein serves to regulate and amplify inflammatory responses. This study aimed to evaluate the expression profile of TREM-1 on the surface of neutrophils from patients with VL at varying time points during leishmanicidal treatment. For this purpose, neutrophils were isolated from the peripheral blood of patients with VL at different stages of treatment, which include 0, 7, and 30 days after treatment. Surface TREM-1 expression was assessed by immunophenotyping neutrophil populations. In addition, the association of TREM-1 expression on the surface of neutrophils with clinical and laboratory parameters and serum levels of inflammatory mediators was also evaluated. Results demonstrate a lower surface expression of TREM-1 in VL patients in the absence of treatment. However, increased levels of TREM-1 expression were observed 7 and 30 days after the start of treatment, with levels similar to those of healthy controls. TREM-1 expression was directly correlated with lymphocyte and erythrocyte count and indirectly correlated with spleen and liver size. Furthermore, elevated levels of TREM-1 expression were also correlated with lower serum levels of interleukin (IL)-22. Taken together, these results suggest that infection by Leishmania infantum leads to depressed TREM-1 expression on the neutrophil surface and may contribute to the inflammatory imbalance that characterizes active VL disease.