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HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape

HIV and Schistosoma infections have been individually associated with pulmonary vascular disease. Co-infection with these pathogens is very common in tropical areas, with an estimate of six million people co-infected worldwide. However, the effects of HIV and Schistosoma co-exposure on the pulmonary...

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Autores principales: Medrano-Garcia, Sandra, Morales-Cano, Daniel, Barreira, Bianca, Vera-Zambrano, Alba, Kumar, Rahul, Kosanovic, Djuro, Schermuly, Ralph Theo, Graham, Brian B., Perez-Vizcaino, Francisco, Mathie, Alistair, Savai, Rajkumar, Pullamseti, Soni, Butrous, Ghazwan, Fernández-Malavé, Edgar, Cogolludo, Angel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368261/
https://www.ncbi.nlm.nih.gov/pubmed/35954255
http://dx.doi.org/10.3390/cells11152414
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author Medrano-Garcia, Sandra
Morales-Cano, Daniel
Barreira, Bianca
Vera-Zambrano, Alba
Kumar, Rahul
Kosanovic, Djuro
Schermuly, Ralph Theo
Graham, Brian B.
Perez-Vizcaino, Francisco
Mathie, Alistair
Savai, Rajkumar
Pullamseti, Soni
Butrous, Ghazwan
Fernández-Malavé, Edgar
Cogolludo, Angel
author_facet Medrano-Garcia, Sandra
Morales-Cano, Daniel
Barreira, Bianca
Vera-Zambrano, Alba
Kumar, Rahul
Kosanovic, Djuro
Schermuly, Ralph Theo
Graham, Brian B.
Perez-Vizcaino, Francisco
Mathie, Alistair
Savai, Rajkumar
Pullamseti, Soni
Butrous, Ghazwan
Fernández-Malavé, Edgar
Cogolludo, Angel
author_sort Medrano-Garcia, Sandra
collection PubMed
description HIV and Schistosoma infections have been individually associated with pulmonary vascular disease. Co-infection with these pathogens is very common in tropical areas, with an estimate of six million people co-infected worldwide. However, the effects of HIV and Schistosoma co-exposure on the pulmonary vasculature and its impact on the development of pulmonary vascular disease are largely unknown. Here, we have approached these questions by using a non-infectious animal model based on lung embolization of Schistosoma mansoni eggs in HIV-1 transgenic (HIV) mice. Schistosome-exposed HIV mice but not wild-type (Wt) counterparts showed augmented pulmonary arterial pressure associated with markedly suppressed endothelial-dependent vasodilation, increased endothelial remodeling and vessel obliterations, formation of plexiform-like lesions and a higher degree of perivascular fibrosis. In contrast, medial wall muscularization was similarly increased in both types of mice. Moreover, HIV mice displayed an impaired immune response to parasite eggs in the lung, as suggested by decreased pulmonary leukocyte infiltration, small-sized granulomas, and augmented residual egg burden. Notably, vascular changes in co-exposed mice were associated with increased expression of proinflammatory and profibrotic cytokines, including IFN-γ and IL-17A in CD4(+) and γδ T cells and IL-13 in myeloid cells. Collectively, our study shows for the first time that combined pulmonary persistence of HIV proteins and Schistosoma eggs, as it may occur in co-infected people, alters the cytokine landscape and targets the vascular endothelium for aggravated pulmonary vascular pathology. Furthermore, it provides an experimental model for the understanding of pulmonary vascular disease associated with HIV and Schistosoma co-morbidity.
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spelling pubmed-93682612022-08-12 HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape Medrano-Garcia, Sandra Morales-Cano, Daniel Barreira, Bianca Vera-Zambrano, Alba Kumar, Rahul Kosanovic, Djuro Schermuly, Ralph Theo Graham, Brian B. Perez-Vizcaino, Francisco Mathie, Alistair Savai, Rajkumar Pullamseti, Soni Butrous, Ghazwan Fernández-Malavé, Edgar Cogolludo, Angel Cells Article HIV and Schistosoma infections have been individually associated with pulmonary vascular disease. Co-infection with these pathogens is very common in tropical areas, with an estimate of six million people co-infected worldwide. However, the effects of HIV and Schistosoma co-exposure on the pulmonary vasculature and its impact on the development of pulmonary vascular disease are largely unknown. Here, we have approached these questions by using a non-infectious animal model based on lung embolization of Schistosoma mansoni eggs in HIV-1 transgenic (HIV) mice. Schistosome-exposed HIV mice but not wild-type (Wt) counterparts showed augmented pulmonary arterial pressure associated with markedly suppressed endothelial-dependent vasodilation, increased endothelial remodeling and vessel obliterations, formation of plexiform-like lesions and a higher degree of perivascular fibrosis. In contrast, medial wall muscularization was similarly increased in both types of mice. Moreover, HIV mice displayed an impaired immune response to parasite eggs in the lung, as suggested by decreased pulmonary leukocyte infiltration, small-sized granulomas, and augmented residual egg burden. Notably, vascular changes in co-exposed mice were associated with increased expression of proinflammatory and profibrotic cytokines, including IFN-γ and IL-17A in CD4(+) and γδ T cells and IL-13 in myeloid cells. Collectively, our study shows for the first time that combined pulmonary persistence of HIV proteins and Schistosoma eggs, as it may occur in co-infected people, alters the cytokine landscape and targets the vascular endothelium for aggravated pulmonary vascular pathology. Furthermore, it provides an experimental model for the understanding of pulmonary vascular disease associated with HIV and Schistosoma co-morbidity. MDPI 2022-08-04 /pmc/articles/PMC9368261/ /pubmed/35954255 http://dx.doi.org/10.3390/cells11152414 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Medrano-Garcia, Sandra
Morales-Cano, Daniel
Barreira, Bianca
Vera-Zambrano, Alba
Kumar, Rahul
Kosanovic, Djuro
Schermuly, Ralph Theo
Graham, Brian B.
Perez-Vizcaino, Francisco
Mathie, Alistair
Savai, Rajkumar
Pullamseti, Soni
Butrous, Ghazwan
Fernández-Malavé, Edgar
Cogolludo, Angel
HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape
title HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape
title_full HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape
title_fullStr HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape
title_full_unstemmed HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape
title_short HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape
title_sort hiv and schistosoma co-exposure leads to exacerbated pulmonary endothelial remodeling and dysfunction associated with altered cytokine landscape
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368261/
https://www.ncbi.nlm.nih.gov/pubmed/35954255
http://dx.doi.org/10.3390/cells11152414
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