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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major

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Ricci-Azevedo, Rafael [1] ; Oliveira, Aline Ferreira [1] ; Conrado, Marina C. A. V. [1] ; Carvalho, Fernanda Caroline [1] ; Roque-Barreira, Maria Cristina [1]
Total Authors: 5
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049 Ribeirao Preto, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: PLoS Neglected Tropical Diseases; v. 10, n. 4 APR 2016.
Web of Science Citations: 10

ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1 beta) release; otherwise, transforming growth factor-beta (TGF-beta) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an appropriate molecular template for the construction of an efficient anti-infective agent. (AU)

FAPESP's process: 13/04088-0 - Lectin from pathogens
Grantee:Maria Cristina Roque Antunes Barreira
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 12/13419-7 - Activation and survival of neutrophils induced by ArtinM: signaling pathways and mechanisms that favor protection against intracellular pathogens
Grantee:Rafael Ricci de Azevedo
Support Opportunities: Scholarships in Brazil - Doctorate