<i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells

Endothelial cells represent one of the first cell types encountered by <i>Leishmania</i> promastigotes when inoculated into the skin of the human hosts by the bite of phlebotomine sand flies. However, little is known on their role in the early recruitment of phagocytic cells and in the e...

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Autores principales:	Sarah D’Alessandro, Silvia Parapini, Yolanda Corbett, Roberta Frigerio, Serena Delbue, Annalisa Modenese, Marina Gramiccia, Pasquale Ferrante, Donatella Taramelli, Nicoletta Basilico
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Leishmania</i> promastigotes endothelial cells CXCL8 neutrophils Medicine R
Acceso en línea:	https://doaj.org/article/19daa5ee834947f0b019c423f4dd8c67
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spelling	oai:doaj.org-article:19daa5ee834947f0b019c423f4dd8c672021-11-25T18:37:46Z<i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells10.3390/pathogens101113802076-0817https://doaj.org/article/19daa5ee834947f0b019c423f4dd8c672021-10-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1380https://doaj.org/toc/2076-0817Endothelial cells represent one of the first cell types encountered by <i>Leishmania</i> promastigotes when inoculated into the skin of the human hosts by the bite of phlebotomine sand flies. However, little is known on their role in the early recruitment of phagocytic cells and in the establishment of the infection. Initially, neutrophils, rapidly recruited to the site of promastigotes deposition, phagocytize <i>Leishmania</i> promastigotes, which elude the killing mechanisms of the host cells, survive, and infect other phagocytic cells. Here, we show that <i>Leishmania</i> promastigotes co-incubated with HMEC-1, a microvascular endothelial cell line, exhibited significant morphological changes and loss of infectivity. Moreover, promastigotes of different <i>Leishmania</i> species stimulated the production of CXCL8 by HMEC-1 in a dose- and TLR4-dependent manner. Interestingly, we observed that the conditioned media from <i>Leishmania</i>-stimulated HMEC-1 cells attracted leukocytes, mostly neutrophils, after 2 h of incubation. After 24 h, a higher percentage of monocytes was detected in conditioned media of unstimulated HMEC-1 cells, whereas neutrophils still predominated in conditioned medium from <i>Leishmania</i>-stimulated cells. The same supernatants did not contain CCL5, a chemokine recruiting T cells and monocytes. On the contrary, inhibition of the production of CCL5 induced by TNF-α was seen. These data indicate that the interaction of <i>Leishmania</i> promastigotes with endothelial cells leads to the production of chemokines and the recruitment of neutrophils, which contribute to the establishment of <i>Leishmania</i> infection.Sarah D’AlessandroSilvia ParapiniYolanda CorbettRoberta FrigerioSerena DelbueAnnalisa ModeneseMarina GramicciaPasquale FerranteDonatella TaramelliNicoletta BasilicoMDPI AGarticle<i>Leishmania</i> promastigotesendothelial cellsCXCL8neutrophilsMedicineRENPathogens, Vol 10, Iss 1380, p 1380 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Leishmania</i> promastigotes endothelial cells CXCL8 neutrophils Medicine R
spellingShingle	<i>Leishmania</i> promastigotes endothelial cells CXCL8 neutrophils Medicine R Sarah D’Alessandro Silvia Parapini Yolanda Corbett Roberta Frigerio Serena Delbue Annalisa Modenese Marina Gramiccia Pasquale Ferrante Donatella Taramelli Nicoletta Basilico <i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells
description	Endothelial cells represent one of the first cell types encountered by <i>Leishmania</i> promastigotes when inoculated into the skin of the human hosts by the bite of phlebotomine sand flies. However, little is known on their role in the early recruitment of phagocytic cells and in the establishment of the infection. Initially, neutrophils, rapidly recruited to the site of promastigotes deposition, phagocytize <i>Leishmania</i> promastigotes, which elude the killing mechanisms of the host cells, survive, and infect other phagocytic cells. Here, we show that <i>Leishmania</i> promastigotes co-incubated with HMEC-1, a microvascular endothelial cell line, exhibited significant morphological changes and loss of infectivity. Moreover, promastigotes of different <i>Leishmania</i> species stimulated the production of CXCL8 by HMEC-1 in a dose- and TLR4-dependent manner. Interestingly, we observed that the conditioned media from <i>Leishmania</i>-stimulated HMEC-1 cells attracted leukocytes, mostly neutrophils, after 2 h of incubation. After 24 h, a higher percentage of monocytes was detected in conditioned media of unstimulated HMEC-1 cells, whereas neutrophils still predominated in conditioned medium from <i>Leishmania</i>-stimulated cells. The same supernatants did not contain CCL5, a chemokine recruiting T cells and monocytes. On the contrary, inhibition of the production of CCL5 induced by TNF-α was seen. These data indicate that the interaction of <i>Leishmania</i> promastigotes with endothelial cells leads to the production of chemokines and the recruitment of neutrophils, which contribute to the establishment of <i>Leishmania</i> infection.
format	article
author	Sarah D’Alessandro Silvia Parapini Yolanda Corbett Roberta Frigerio Serena Delbue Annalisa Modenese Marina Gramiccia Pasquale Ferrante Donatella Taramelli Nicoletta Basilico
author_facet	Sarah D’Alessandro Silvia Parapini Yolanda Corbett Roberta Frigerio Serena Delbue Annalisa Modenese Marina Gramiccia Pasquale Ferrante Donatella Taramelli Nicoletta Basilico
author_sort	Sarah D’Alessandro
title	<i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells
title_short	<i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells
title_full	<i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells
title_fullStr	<i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells
title_full_unstemmed	<i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells
title_sort	<i>leishmania</i> promastigotes enhance neutrophil recruitment through the production of cxcl8 by endothelial cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/19daa5ee834947f0b019c423f4dd8c67
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<i>Leishmania</i> Promastigotes Enhance Neutrophil Recruitment through the Production of CXCL8 by Endothelial Cells

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