Crosstalk between purinergic receptors and lipid mediators in leishmaniasis

Chaves, Mariana M.; Canetti, Cláudio; Coutinho‐Silva, Robson

doi:10.1186/s13071-016-1781-1

Cited by 21 publications

(21 citation statements)

References 140 publications

(120 reference statements)

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“…The purinergic network signaling of immune cells senses small changes in the concentration of extracellular nucleotides. These responses play multiple roles in immunoregulation by stimulating lymphocytes proliferation, ROS and NO generation, and cytokines and chemokine secretion ( 9 , 28 , 29 ). This study now shows that L. infantum exerts NTPDase activity.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, Leishmania sp. is able to modulate the concentration of extracellular nucleotides, affecting the balance of pro- vs. anti-inflammatory molecules, and thus allowing evasion of host immune responses ( 9 ). For example, the blockage of the purinergic adenosine receptor causes decreased lesion size and parasitism in tegumentary leishmaniais ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, Leishmania sp. is able to modulate the concentration of extracellular nucleotides, thereby altering the balance of pro- and anti-inflammatory molecules to evade host immune responses ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

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Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto-Nucleotidases

et al. 2018

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Ecto-nucleotidase activity is involved in the infection process of Leishmania and various other parasites that enables modulation of host immune responses to promote disease progression. One of the enzymes responsible for this activity is the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase). The enzyme hydrolyzes nucleotides tri- and/or di-phosphate into monophosphate products, which are subsequently hydrolyzed into adenosine. These nucleotides can serve as purinergic signaling molecules involved in diverse cellular processes that govern immune responses. Given the importance of the extracellular metabolism of these nucleotides during intracellular pathogen infections, this study evaluates the role of ecto-nucleotidase activity during Leishmania infantum (L. infantum) infection in human macrophages. E-NTPDase protein expression and activity was evaluated in L. infantum during purine starvation, adenosine-enriched medium, or in the presence of an inhibitor of ecto-nucleotidases. Results show that E-NTPDase is expressed in L. infantum parasites, including on the cell membrane. Furthermore, functional activity of the enzyme was modulated according to the availability of adenosine in the medium. Purine starvation increased the hydrolytic capacity of nucleotides leading to higher infectivity, while growth in adenosine-enriched medium led to lower infectivity. Moreover, inhibiting E-NTPDase function decreased L. infantum infection in macrophages, suggesting the enzyme may serve as a ligand. Taken together, the ability of L. infantum to hydrolyze nucleotides is directly associated with increased infectivity in macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto-Nucleotidases

et al. 2018

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“…This is because of the emergence of antibiotic resistant strains of different bacteria against the prevailing drugs that has spread all over the world (Davies and Davies, 2010). Moreover, pathogens have also evolved many strategies to circumvent host immune defences and in turn induce excessive inflammation resulting in the injury of host tissue (Chaves et al, 2016;Gomes et al, 2016). Hence, to tackle this situation efficiently, discovery of new antimicrobial drugs that can modulate the host immune response upon microbial infection without directly targeting the microbes is urgently needed.…”

Section: Immune Response Mediated By Plant Lectinsmentioning

confidence: 99%

Structure-function and application of plant lectins in disease biology and immunity

Mishra

Behura

Mawatwal

et al. 2019

Food and Chemical Toxicology

154

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A B S T R A C TLectins are proteins with a high degree of stereospecificity to recognize various sugar structures and form reversible linkages upon interaction with glyco-conjugate complexes. These are abundantly found in plants, animals and many other species and are known to agglutinate various blood groups of erythrocytes. Further, due to the unique carbohydrate recognition property, lectins have been extensively used in many biological functions that make use of protein-carbohydrate recognition like detection, isolation and characterization of glycoconjugates, histochemistry of cells and tissues, tumor cell recognition and many more. In this review, we have summarized the immunomodulatory effects of plant lectins and their effects against diseases, including antimicrobial action. We found that many plant lectins mediate its microbicidal activity by triggering host immune responses that result in the release of several cytokines followed by activation of effector mechanism. Moreover, certain lectins also enhance the phagocytic activity of macrophages during microbial infections. Lectins along with heat killed microbes can act as vaccine to provide long term protection from deadly microbes. Hence, lectin based therapy can be used as a better substitute to fight microbial diseases efficiently in future.

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“…This fact critically reduces the shelf life of antibiotics that are not efficient to combat the emerging multidrug-resistant strains ( Holmes et al, 2016 ; Laxminarayan et al, 2016 ). In addition, pathogens have developed several mechanisms to evade and suppress the host defenses and/or to induce exacerbated inflammation (which may cause host tissue injury) ( Chaves et al, 2016 ; Gomes et al, 2016 ; Ko, 2016 ; Malachowski et al, 2016 ; Sha et al, 2017 ). This scenario encourages the development of new approaches to treat microbial infection, such as those based on the modulation of the host immune system.…”

Section: Introductionmentioning

confidence: 99%

Targeting the Immune System with Plant Lectins to Combat Microbial Infections

et al. 2017

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The arsenal of drugs available to treat infections caused by eukaryotic and prokaryotic microbes has been declining exponentially due to antimicrobial resistance phenomenon, leading to an urgent need to develop new therapeutic strategies. Host-directed immunotherapy has been reported as an attractive option to treat microbial infections. It consists in the improvement of host defenses by increasing the expression of inflammatory mediators and/or controlling of inflammation-induced tissue injury. Although the in vitro antimicrobial and immunomodulatory activities of lectins have been extensively demonstrated, few studies have evaluated their in vivo effects on experimental models of infections. This review aims to highlight the experimental use of immunomodulatory plant lectins to improve the host immune response against microbial infections. Lectins have been used in vivo both prophylactically and therapeutically resulting in the increased survival of mice under microbial challenge. Other studies successfully demonstrated that lectins could be used in combination with parasite antigens in order to induce a more efficient immunization. Therefore, these plant lectins represent new candidates for management of microbial infections. Furthermore, immunotherapeutic studies have improved our knowledge about the mechanisms involved in host–pathogen interactions, and may also help in the discovery of new drug targets.

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Crosstalk between purinergic receptors and lipid mediators in leishmaniasis

Cited by 21 publications

References 140 publications

Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto-Nucleotidases

Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto-Nucleotidases

Structure-function and application of plant lectins in disease biology and immunity

Targeting the Immune System with Plant Lectins to Combat Microbial Infections

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