Abstract
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-1β) release; otherwise, transforming growth factor-beta (TGF-β) 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.
Highlights
Global immunization regimes have eradicated smallpox and controlled a large number of other infections [1,2]
Our primary model is ArtinM, from the seeds of jackfruit, a lectin that binds to TLR2 sugar chains on macrophages and dendritic cells and promotes production of cytokines that engages T lymphocytes in a process that culminate with elimination of intracellular pathogens
ArtinM activates other immune cells, including neutrophils, which contributes to the pathogen elimination, but may account for tissue damage
Summary
Global immunization regimes have eradicated smallpox and controlled a large number of other infections [1,2]. Vaccines have been successful against infections caused by extracellular pathogens or those whose pathogenesis is mediated by toxins Under these circumstances, vaccines confer protection by inducing antibodies that neutralize the inoculum and prevent the establishment of infections [3]. A research field has emerged that concerns the development of alternative prophylactic or therapeutic agents to enhance host cellular response In this context, agonists of innate immunity receptors, especially Toll-like receptors (TLRs), provide promising approaches [5]. The interaction of agonists with TLRs triggers cell signaling and production of inflammatory and anti-inflammatory mediators [6] This process, beyond inducing early mechanisms of host defense, primes and orchestrates antigen-specific adaptive responses [7]. The ability of activated TLRs to modulate adaptive immunity motivates ongoing trials of new drugs based on natural or synthetic TLR ligands for infectious diseases in humans [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
