Article
Leishmania infantumInduces the Release of sTREM-1 in Visceral Leishmaniasis
Registro en:
BOMFIM, L. G. S. et al. Leishmania infantumInduces the Release of sTREM-1 in Visceral Leishmaniasis. Frontiers in Microbiology, v. 8, Article 2265, 2017.
1664-302X
10.3389/fmicb.2017.02265
Autor
Bomfim, Lays Gisele Santos
Magalhães, Lucas S
Santos Filho, Marcello Augusto Anchieta
Peres, Nalu Teixeira de Aguiar
Corrêa, Cristiane B
Tanajura, Diego Moura
Silva, Angela Maraia da
Lipscomb, Michael W
Borges, Valéria de Matos
Jesus, Amélia Ribeiro de
Almeida, Roque Pacheco de
Moura, Tatiana Rodrigues de
Resumen
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), MCTI/CNPQ/Universal 14/2014—460743/2014-7 (TdM) and PROCAD/CASADINHO—n◦552721/2011-5 (RA); Fundação de
Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe FAPITEC/SE/FUNTEC/CNPq n◦12/2009—019.203.02712/2009-8 (AJ); Coordenação de Aperfeiçoamento de Pessoal de Nível
Superior (CAPES), Programa Nacional de Incentivo à Pesquisa em Parasitologia Básica, Edital No 032/2010 (AJ); National Institute Health, NIH Grant# SC2GM103741 (ML); Department of Defense, DOD Grant# W911NF-14-1-0123, (ML); and National Science Foundation, NSF Grant# 1428768, (ML). 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 exposurein vitrotoLeishmania infantummodulates 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 thatL. infantummay modulate TREM-1 in neutrophils and high levels of this molecule is associated with severe VL.