Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/56042 http://dx.doi.org/10.3389/fmicb.2016.00580 |
Resumo: | Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a human systemic mycosis with worldwide distribution. In the present work, we demonstrate that H. capsulatum yeasts are able to induce cytokine secretion by the human lung epithelial cell line A549 in integrin- and Src-family kinase (SFK)-dependent manners. This conclusion is supported by small interfering RNA (siRNA) directed to alpha 3 and alpha 5 integrins, and PP2, an inhibitor of SFK activation. siRNA and PP2 reduced IL-6 and IL-8 secretion in H. capsulatum-infected A549 cell cultures. In addition, alpha 3 and alpha 5 integrins from A549 cells were capable of associating with H. capsulatum yeasts, and this fungus promotes recruitment of these integrins and SFKs to A549 cell membrane rafts. Corroborating this finding, membrane raft disruption with the cholesterol-chelator methyl-beta-cyclodextrin reduced the levels of integrins and SFKs in these cell membrane domains. Finally, pretreatment of A549 cells with the cholesterol binding compound, and also a membrane raft disruptor, filipin, significantly reduced IL-6 and IL-8 levels in A549-H.capsulatum cultures. Taken together, these results indicate that H. capsulatum yeasts induce secretion of IL-6 and IL-8 in human lung epithelial cells by interacting with alpha 3 and alpha 5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation. |
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Maza, Paloma Korehisa [UNIFESP]Suzuki, Erika [UNIFESP]2020-07-22T13:23:06Z2020-07-22T13:23:06Z2016Frontiers In Microbiology. Lausanne, v. 7, p. -, 2016.1664-302Xhttps://repositorio.unifesp.br/handle/11600/56042http://dx.doi.org/10.3389/fmicb.2016.00580WOS000374596000001.pdf10.3389/fmicb.2016.00580WOS:000374596000001Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a human systemic mycosis with worldwide distribution. In the present work, we demonstrate that H. capsulatum yeasts are able to induce cytokine secretion by the human lung epithelial cell line A549 in integrin- and Src-family kinase (SFK)-dependent manners. This conclusion is supported by small interfering RNA (siRNA) directed to alpha 3 and alpha 5 integrins, and PP2, an inhibitor of SFK activation. siRNA and PP2 reduced IL-6 and IL-8 secretion in H. capsulatum-infected A549 cell cultures. In addition, alpha 3 and alpha 5 integrins from A549 cells were capable of associating with H. capsulatum yeasts, and this fungus promotes recruitment of these integrins and SFKs to A549 cell membrane rafts. Corroborating this finding, membrane raft disruption with the cholesterol-chelator methyl-beta-cyclodextrin reduced the levels of integrins and SFKs in these cell membrane domains. Finally, pretreatment of A549 cells with the cholesterol binding compound, and also a membrane raft disruptor, filipin, significantly reduced IL-6 and IL-8 levels in A549-H.capsulatum cultures. Taken together, these results indicate that H. capsulatum yeasts induce secretion of IL-6 and IL-8 in human lung epithelial cells by interacting with alpha 3 and alpha 5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation.Brazilian agencies: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilFAPESP: 2011/22773-6FAPESP: 2012/11792-2Web of Science-engFrontiers Media SaFrontiers In MicrobiologyHistoplasma capsulatumfungiepithelial cellscytokineintegrinmembrane raftsSrc-family kinasesHistoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitmentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLausanne7info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000374596000001.pdfapplication/pdf955672${dspace.ui.url}/bitstream/11600/56042/1/WOS000374596000001.pdf2370a85614d86538398a4f485a171234MD51open accessTEXTWOS000374596000001.pdf.txtWOS000374596000001.pdf.txtExtracted texttext/plain60607${dspace.ui.url}/bitstream/11600/56042/2/WOS000374596000001.pdf.txtac175c70c9353dd0b36b3b1c433ca798MD52open accessTHUMBNAILWOS000374596000001.pdf.jpgWOS000374596000001.pdf.jpgIM Thumbnailimage/jpeg6642${dspace.ui.url}/bitstream/11600/56042/4/WOS000374596000001.pdf.jpg6066678319b4516221b471622f4b8ee1MD54open access11600/560422022-08-01 01:27:32.647open accessoai:repositorio.unifesp.br:11600/56042Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-08-01T04:27:32Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment |
title |
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment |
spellingShingle |
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment Maza, Paloma Korehisa [UNIFESP] Histoplasma capsulatum fungi epithelial cells cytokine integrin membrane rafts Src-family kinases |
title_short |
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment |
title_full |
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment |
title_fullStr |
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment |
title_full_unstemmed |
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment |
title_sort |
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment |
author |
Maza, Paloma Korehisa [UNIFESP] |
author_facet |
Maza, Paloma Korehisa [UNIFESP] Suzuki, Erika [UNIFESP] |
author_role |
author |
author2 |
Suzuki, Erika [UNIFESP] |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Maza, Paloma Korehisa [UNIFESP] Suzuki, Erika [UNIFESP] |
dc.subject.eng.fl_str_mv |
Histoplasma capsulatum fungi epithelial cells cytokine integrin membrane rafts Src-family kinases |
topic |
Histoplasma capsulatum fungi epithelial cells cytokine integrin membrane rafts Src-family kinases |
description |
Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a human systemic mycosis with worldwide distribution. In the present work, we demonstrate that H. capsulatum yeasts are able to induce cytokine secretion by the human lung epithelial cell line A549 in integrin- and Src-family kinase (SFK)-dependent manners. This conclusion is supported by small interfering RNA (siRNA) directed to alpha 3 and alpha 5 integrins, and PP2, an inhibitor of SFK activation. siRNA and PP2 reduced IL-6 and IL-8 secretion in H. capsulatum-infected A549 cell cultures. In addition, alpha 3 and alpha 5 integrins from A549 cells were capable of associating with H. capsulatum yeasts, and this fungus promotes recruitment of these integrins and SFKs to A549 cell membrane rafts. Corroborating this finding, membrane raft disruption with the cholesterol-chelator methyl-beta-cyclodextrin reduced the levels of integrins and SFKs in these cell membrane domains. Finally, pretreatment of A549 cells with the cholesterol binding compound, and also a membrane raft disruptor, filipin, significantly reduced IL-6 and IL-8 levels in A549-H.capsulatum cultures. Taken together, these results indicate that H. capsulatum yeasts induce secretion of IL-6 and IL-8 in human lung epithelial cells by interacting with alpha 3 and alpha 5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2020-07-22T13:23:06Z |
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2020-07-22T13:23:06Z |
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dc.identifier.citation.fl_str_mv |
Frontiers In Microbiology. Lausanne, v. 7, p. -, 2016. |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/56042 http://dx.doi.org/10.3389/fmicb.2016.00580 |
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1664-302X |
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WOS000374596000001.pdf |
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10.3389/fmicb.2016.00580 |
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WOS:000374596000001 |
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Frontiers In Microbiology. Lausanne, v. 7, p. -, 2016. 1664-302X WOS000374596000001.pdf 10.3389/fmicb.2016.00580 WOS:000374596000001 |
url |
https://repositorio.unifesp.br/handle/11600/56042 http://dx.doi.org/10.3389/fmicb.2016.00580 |
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