Leishmania infantum Induces the Release of sTREM-1 in Visceral Leishmaniasis

• Main Authors: Lays G. S. Bomfim, Lucas S. Magalhães, Marcello A. A. Santos-Filho, Nalu T. A. Peres, Cristiane B. Corrêa, Diego M. Tanajura, Angela M. Silva, Michael W. Lipscomb, Valéria M. Borges, Amélia R. Jesus, Roque P. Almeida, Tatiana R. de Moura
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-11-01
• Series: Frontiers in Microbiology
• Subjects: visceral leishmaniasis; Leishmania infantum; neutrophils; sTREM-1; TREM-1
• Online Access: http://journal.frontiersin.org/article/10.3389/fmicb.2017.02265/full

Visceral leishmaniasis (VL) is a systemic transmissible disease that remains to be a major global health problem. The inflammatory response during VL is characterized by the release of several cytokines and other pro-inflammatory mediators. Triggering Receptor Expressed on Myeloid Cells (TREM) are a group of evolutionarily conserved membrane-bound surface receptors expressed on neutrophils and monocytes. Engagement of TREM-1 directs intracellular signaling events that drive cytokine production, degranulation, and phagocytosis. In certain inflammatory-associated diseases, TREM-1 can also be found as a soluble form (sTREM-1), which can negatively regulate TREM-1 receptor signaling. In these studies, we now find that high levels of circulating sTREM-1 correlate directly with VL disease severity. In particular, high levels of sTREM-1 were observed in non-survivor VL patients. Furthermore, these levels of sTREM-1 positively correlated with liver size and negatively correlated with leukocyte counts and hemoglobin concentration. Moreover, we found that neutrophils exposure in vitro to Leishmania infantum modulates TREM-1, DAP12, and IL-8 gene expression, while also increasing release of sTREM-1. Finally, results revealed that higher sTREM-1 levels are associated with increasing parasite ratio. Taken together, these studies suggest that L. infantum may modulate TREM-1 in neutrophils and high levels of this molecule is associated with severe VL.