Exposure of phosphatidylserine on Leishmania amazonensis isolates is associated with diffuse cutaneous leishmaniasis and parasite infectivity

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of leishmaniasis, characterized by an inefficient parasite-specific cellular response and heavily parasitized macrophages. In Brazil, Leishmania (Leishmania) amazonensis is the main species involved in DCL cases. In the experimen...

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Published in:	PloS one Vol. 7; no. 5; p. e36595
Main Authors:	França-Costa, Jaqueline, Wanderley, João Luiz Mendes, Deolindo, Poliana, Zarattini, Jessica B, Costa, Jackson, Soong, Lynn, Barcinski, Marcello André, Barral, Aldina, Borges, Valeria M
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 04-05-2012 Public Library of Science (PLoS)
Subjects:	Amastigotes Analysis Animals Apoptosis Biology Cell survival Chronic Disease Chronic diseases Chronic illnesses Cutaneous leishmaniasis Cytokines Cytokines - biosynthesis Dendritic cells Dose-Response Relationship, Drug Experimental infection Exposure Health aspects Humans Immune response Immune system Immune Tolerance - drug effects Immunology Immunosurveillance Infections Infectivity Inflammation Inflammatory response Leishmania Leishmania - drug effects Leishmania - isolation & purification Leishmania - pathogenicity Leishmania amazonensis Leishmania major Leishmaniasis, Diffuse Cutaneous - immunology Leishmaniasis, Diffuse Cutaneous - parasitology Lesions Macrophages Macrophages - drug effects Macrophages - metabolism Macrophages - parasitology Medical research Medicine Mice Neutrophils Nitric oxide Parasites Parasitic diseases Pathogenesis Patients Peritoneum Phosphatidylserine Phosphatidylserines - pharmacology Phospholipids Vacuoles Vector-borne diseases Brazil Rio de Janeiro Brazil
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Summary:	Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of leishmaniasis, characterized by an inefficient parasite-specific cellular response and heavily parasitized macrophages. In Brazil, Leishmania (Leishmania) amazonensis is the main species involved in DCL cases. In the experimental model, recognition of phosphatidylserine (PS) molecules exposed on the surface of amastigotes forms of L. amazonensis inhibits the inflammatory response of infected macrophages as a strategy to evade the host immune surveillance. In this study, we examined whether PS exposure on L. amazonensis isolates from DCL patients operated as a parasite pathogenic factor and as a putative suppression mechanism of immune response during the infection. Peritoneal macrophages from F1 mice (BALB/c×C57BL/6) were infected with different L. amazonensis isolates from patients with localized cutaneous leishmaniasis (LCL) or DCL. DCL isolates showed higher PS exposure than their counterparts from LCL patients. In addition, PS exposure was positively correlated with clinical parameters of the human infection (number of lesions and time of disease) and with characteristics of the experimental infection (macrophage infection and anti-inflammatory cytokine induction). Furthermore, parasites isolated from DCL patients displayed an increased area in parasitophorous vacuoles (PV) when compared to those isolated from LCL patients. Thus, this study shows for the first time that a parasite factor (exposed PS) might be associated with parasite survival/persistence in macrophages and lesion exacerbation during the course of DCL, providing new insights regarding pathogenic mechanism in this rare chronic disease.
Bibliography:	Conceived and designed the experiments: JFC JLMW PD LS MAB AB VMB. Performed the experiments: JFC JLMW PD JBZ. Analyzed the data: JFC JLMW PD LS MAB JC AB VMB. Contributed reagents/materials/analysis tools: JC LS MAB AB VMB. Wrote the paper: JFC JLMW LS MAB VMB.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0036595