Purinergic signaling and infection by Leishmania : A new approach to evasion of the immune response

Abstract

Infection by protozoan parasites is part of the most common Tropical Neglected Diseases. In the case of leishmaniasis, several millions of people are at risk of contracting the disease. In spite of innumerous studies that elucidated the immune response capable of killing the parasite, the understanding of the evasion mechanisms utilized by the parasite to survive within the very cell responsible for its destruction is still incomplete. In this review, we offer a new approach to the control of the immune response against the parasite. The ability of the parasite to modulate the levels of extracellular ATP and adenosine either by directly acting on the levels of these molecules or by inducing the expression of CD39 and CD73 on the infected cell may influence the magnitude of the immune response against the parasite contributing to its growth and survival.

Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis

“…PSG is a mucin-like gel produced by promastigotes in the sandflies that accumulates in and blocks the vector mouthparts, forcing the infected sandflies to regurgitate several times during blood feeding, a behavior hypothesized to enhance the chances of parasite transmission and inflammation [6,28]. In addition to their contribution to preventing the formation of blood clots, the hydrolysis of ATP by vector-derived nucleotidases followed by increased levels of extracellular AMP and adenosine have been suggested to exacerbate lesions in experimental models of leishmaniasis, most likely through activation of the purinergic receptor A 2A on immune cells, leading to inhibition of inflammatory functions, such as monocyte maturation, phagocytosis, and nitric oxide (NO) production [29].…”

“…Microorganisms 2019, 7, 695 4 of 25 purinergic receptor A2A on immune cells, leading to inhibition of inflammatory functions, such as monocyte maturation, phagocytosis, and nitric oxide (NO) production [29]. An additional explanation for the large and sustained neutrophil infiltration at the bite sites was recently proposed and involves the immunomodulatory properties of gut microbes from infected sandflies that are co-egested with Leishmania parasites into the skin (Figure 1).…”

“…Nucleotidases: both parasite and vector-derived nucleotidases can modulate purinergic signaling mechanisms through increased generation of adenosine, which stimulates the production of IL-10 and inhibits inflammatory functions in neutrophils, DCs, and macrophages [29,78]. Enhanced activity of nucleotidases has been correlated with higher virulence of several Leishmania spp.…”

The inflammasome: Friend or foe in Chlamydia infection?

“…Purinergic signaling is a highly conserved form of cell–cell communication involving extracellular ATP, adenosine and other purines. It plays a key role in modulating inflammatory responses, and as such many pathogens have developed to mechanisms to manipulate the pathway to their advantage [17] , [18] , [19] . In this issue of the Biomedical Journal , Silva [20] reviews another example of this interplay involving the parasitic worm Schistosoma .…”

Perturbing purinergic signaling: A pathogen's guidebook to counteracting inflammatory responses

“…It should thus come as no surprise that many human pathogens are able to manipulate this signaling pathway to their advantage. This issue of the Biomedical Journal includes three reviews describing the evasive tactics of three of such pathogens, Trichomonas vaginalis [1] , Leishmania [2] and Porphyromonas gingivalis [3] .…”