Glycoconjugates in New World species of Leishmania: Polymorphisms in lipophosphoglycan and glycoinositolphospholipids and interaction with hosts

Assis, Rafael Ramiro de; Ibraim, Izabela Coimbra; Nogueira, Paula Monalisa; Soares, Rodrigo Pedro; Turco, Salvatore J.

doi:10.1016/j.bbagen.2011.11.001

Cited by 92 publications

(107 citation statements)

References 153 publications

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“…It is well known that Leishmania growth and persistence are associated with the subversion of macrophage immune response (41,(44)(45)(46). However, it was demonstrated that is possible to FN-activated neutrophils (FN-PMN).…”

Section: Discussionmentioning

confidence: 99%

Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites

Tavares

Afonso

Suarez

et al. 2016

The Journal of Immunology

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Neutrophils mediate early responses against pathogens, and they become activated during endothelial transmigration toward the inflammatory site. In the current study, human neutrophils were activated in vitro with immobilized extracellular matrix proteins, such as fibronectin (FN), collagen, and laminin. Neutrophil activation by FN, but not other extracellular matrix proteins, induces the release of the granules’ contents, measured as matrix metalloproteinase 9 and neutrophil elastase activity in culture supernatant, as well as reactive oxygen species production. Upon contact with Leishmania amazonensis–infected macrophages, these FN-activated neutrophils reduce the parasite burden through a mechanism independent of cell contact. The release of granule proteases, such as myeloperoxidase, neutrophil elastase, and matrix metalloproteinase 9, activates macrophages through TLRs, leading to the production of inflammatory mediators, TNF-α and leukotriene B4 (LTB4), which are involved in parasite killing by infected macrophages. The pharmacological inhibition of degranulation reverted this effect, abolishing LTB4 and TNF production. Together, these results suggest that FN-driven degranulation of neutrophils induces the production of LTB4 and TNF by infected macrophages, leading to the control of Leishmania infection.

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Section: Discussionmentioning

confidence: 99%

Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites

Tavares

Afonso

Suarez

et al. 2016

The Journal of Immunology

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“…Additionally, our group showed that Leishmania amazonensis and its LPG can activate NETosis (12). LPG is a glycolipid expressed on the promastigote membrane in all species of Leishmania, presenting high polymorphism among species and strains (44,45). Leishmania parasites seem to induce NETs faster than other stimuli studied.…”

Section: Discussionmentioning

confidence: 99%

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

et al. 2014

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Leishmaniasis is a widespread neglected tropical disease caused by parasites of the Leishmania genus. These parasites express the enzyme 3=-nucleotidase/nuclease (3=NT/NU), which has been described to be involved in parasite nutrition and infection. Bacteria that express nucleases escape the toxic effects of neutrophil extracellular traps (NETs). Hence, we investigated the role of 3=NT/NU in Leishmania survival of NET-mediated killing. Promastigotes of Leishmania infantum were cultured in high-phosphate (HP) or low-phosphate (LP) medium to modulate nuclease activity. We compared the survival of the two different groups of Leishmania during interaction with human neutrophils, assessing the role of neutrophil extracellular traps. As previously reported, we detected higher nuclease activity in parasites cultured in LP medium. Both LP and HP promastigotes were capable of inducing the release of neutrophil extracellular traps from human neutrophils in a dose-and time-dependent manner. LP parasites had 2.4 times more survival than HP promastigotes. NET disruption was prevented by the treatment of the parasites with ammonium tetrathiomolybdate (TTM), a 3=NT/NU inhibitor. Inhibition of 3=NT/NU by 3=-AMP, 5=-GMP, or TTM decreased promastigote survival upon interaction with neutrophils. Our results show that Leishmania infantum induces NET release and that promastigotes can escape NET-mediated killing by 3=-nucleotidase/nuclease activity, thus ascribing a new function to this enzyme. N eutrophils are short-lived cells and the most abundant leukocytes in the blood circulation; they constitute one of the first lines of defense against invading microorganisms (1). These granulocytes can kill microorganisms by phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are weblike structures composed of chromatin, granules, and cytoplasmic proteins that are extruded when neutrophils undergo NETosis, a unique cell death mechanism (2-5). However, recent work challenges NETosis as a cell death mechanism because live neutrophils were detected after NET extrusion in in vivo studies (6). NETs function by killing and containing pathogens, thereby preventing the pathogen's dissemination through the organism. In addition, some studies have indicated that NETs play a role in autoimmune diseases (7-10).A diverse group of stimuli has been described as activating NETosis (5, 11). Among the parasites, Leishmania promastigotes were demonstrated to activate release of NETs (12, 13). Leishmania amazonensis promastigotes interact intimately with NETs and are killed by web-associated histones (12). However, although promastigotes of Leishmania donovani trigger NET release, these parasites escape the toxicity of NETs (13). Groups of microorganisms have evolved different mechanisms of escaping the toxic effects of NETs. Streptococcus pneumoniae, group A Streptococcus, Streptococcus agalactiae, Staphylococcus aureus, and Vibrio cholerae express endonucleases that efficiently degrade DNA filaments from NETs, allowing these bacteria...

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“…Otros estudios realizados en el subgénero Leishmania, revelan que durante la metaciclogénesis, el lipofosfoglicano (LPG), un glicolípido presente también en la superficie de los promastigotes del parásito que interactúa con la superficie epitelial del intestino medio permitiendo su adhesión, sufre modificaciones estructurales en sus cadenas laterales que involucran a monosacáridos, en el caso de Leishmania (L.) major involucra a una hexosa (galactosa) y a una pentosa (arabinosa) (18) , y en L. (V.) braziliensis, se ha reportado que el LPG se encuentra en menor cantidad en comparación a las especies del subgénero Leishmania, pero al igual que en estas, las formas promastigotes cuentan con una Capacidad infectiva en leishmania mayor proporción de estas moléculas en comparación de las formas metacíclicas. Mediante pruebas inmunohistoquímicas se demostró que el LPG en las formas promastigotes procíclicas y metacíclicas que se encuentran adheridas al epitelio del intestino medio del vector, cuentan con residuos de β(1,3)glucosa; otras modificaciones que han sido involucradas en esta interacción del parásito con el vector son la galactosa, la manosa y la glucosa (19,20) . La transformación de promastigotes procíclicos a metacíclicos involucra modificaciones bioquímicas, moleculares y genéticas que proporcionan al promastigote metacíclico resistencia a la lisis mediada por el complemento (21,22) , facilitan el proceso de fagocitosis por los macrófagos (22) , aseguran la supervivencia del parásito en condiciones adversas en el fagolisosoma del macrófago, inducen la formación de proteínas de la familia de las quinasas y regulan la producción del óxido nítrico en las vacuolas fagocitóforas (20,23) .…”

Section: Introductionunclassified

“…Mediante pruebas inmunohistoquímicas se demostró que el LPG en las formas promastigotes procíclicas y metacíclicas que se encuentran adheridas al epitelio del intestino medio del vector, cuentan con residuos de β(1,3)glucosa; otras modificaciones que han sido involucradas en esta interacción del parásito con el vector son la galactosa, la manosa y la glucosa (19,20) . La transformación de promastigotes procíclicos a metacíclicos involucra modificaciones bioquímicas, moleculares y genéticas que proporcionan al promastigote metacíclico resistencia a la lisis mediada por el complemento (21,22) , facilitan el proceso de fagocitosis por los macrófagos (22) , aseguran la supervivencia del parásito en condiciones adversas en el fagolisosoma del macrófago, inducen la formación de proteínas de la familia de las quinasas y regulan la producción del óxido nítrico en las vacuolas fagocitóforas (20,23) .…”

Section: Introductionunclassified

Capacidad infectiva de promastigotes en fase estacionaria de Leishmania (Viannia) braziliensis y Leishmania (Viannia) peruviana, en línea celular DH82

Calvay-Sánchez

Rojas-Palomino

Sandoval-Juárez

et al. 2015

Rev Peru Med Exp Salud Publica

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RESUMENObjetivos. Determinar la capacidad infectiva de los promastigotes de Leishmania (V.) peruviana y Leishmania (V.) braziliensis en la línea celular macrófago-monocítica de Canis familiaris DH82. Materiales y métodos. Se realizó un estudio experimental durante los meses de enero a diciembre de 2013. Se utilizaron cepas referenciales de Leishmania (V.) braziliensis MHOM/PE/84/LC53 y Leishmania (V.) peruviana MHOM/PE/84/LC26. La línea celular fue infectada con promastigotes en fase estacionaria y la capacidad infectiva fue determinada como el producto del porcentaje de macrófagos infectados por el promedio de amastigotes por macrófago infectado, observado al microscopio de epifluorescencia. Resultados. El 13% de formas metacíclicas para Leishmania (V.) braziliensis correspondió al día 17,5 posinoculación y para Leishmania (V.) peruviana un porcentaje de 9,5% en el día 14,5. No se encontró diferencia significativa entre la capacidad infectiva de los promastigotes en fase estacionaria de ambas especies. Conclusiones. Se recomienda evaluar la capacidad infectiva de los promastigotes metacíclicos de cepas de Leishmania (V.) peruviana y Leishmania (V.) braziliensis en líneas celulares, a fin de determinar el modelo de infección in vitro más adecuado, que permita efectuar estudios de susceptibilidad a las drogas leishmanicidas de mayor eficacia para el control de la enfermedad. Palabras clave: Leishmaniasis; Virulencia; Línea celular, Leishmania braziliensis (fuente: DeCS BIREME). INFECTIVITY OF PROMASTIGOTES IN STATIONARY PHASE OF Leishmania (Viannia) braziliensis AND Leishmania (Viannia) peruviana, IN CELL LINE DH82 ABSTRACTObjectives. To determine the infectivity of promastigotes of Leishmania (V.) peruviana and Leishmania (V.) braziliensis in monocyte-macrophage cell line DH82 of Canis familiaris. Materials and methods. Was conducted a experimental study during the months of january to december 2013. Were used strains of Leishmania were used (V.) braziliensis MHOM / PE / 84 / LC53 and Leishmania (V.) peruviana MHOM / PE / 84 / LC26. The cell line was infected with stationary phase promastigotes and infectivity was determined as the product of percent infected macrophages average amastigotes per macrophage observed in epifluorescence microscope. Results. 13% of metacyclic forms to Leishmania (V.) braziliensis corresponded to 17.5 days post inoculation and Leishmania (V.) peruviana a percentage of 9.5% on the day 14.5. No significant difference was found between infectivity of stationary phase promastigotes of both species. Conclusions. It is recommended assess the infectivity of metacyclic promastigotes peruviana strains of Leishmania (V.) and Leishmania (V.) braziliensis cell lines in order to determine the most appropriate model in vitro infection, allowing leishmanicidas make the drug more effective susceptibility studies for disease control.

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Glycoconjugates in New World species of Leishmania: Polymorphisms in lipophosphoglycan and glycoinositolphospholipids and interaction with hosts

Cited by 92 publications

References 153 publications

Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites

Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

Capacidad infectiva de promastigotes en fase estacionaria de Leishmania (Viannia) braziliensis y Leishmania (Viannia) peruviana, en línea celular DH82

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