Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment

Página do item simplificado
dc.citation.volume7
dc.contributor.authorMaza, Paloma Korehisa [UNIFESP]
dc.contributor.authorSuzuki, Erika [UNIFESP]
dc.coverageLausanne
dc.date.accessioned2020-07-22T13:23:06Z
dc.date.available2020-07-22T13:23:06Z
dc.date.issued2016
dc.description.abstractHistoplasma 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.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipBrazilian agencies: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.description.sponsorshipIDFAPESP: 2011/22773-6
dc.description.sponsorshipIDFAPESP: 2012/11792-2
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fmicb.2016.00580
dc.identifier.citationFrontiers In Microbiology. Lausanne, v. 7, p. -, 2016.
dc.identifier.doi10.3389/fmicb.2016.00580
dc.identifier.fileWOS000374596000001.pdf
dc.identifier.issn1664-302X
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56042
dc.identifier.wosWOS:000374596000001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Microbiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHistoplasma capsulatumen
dc.subjectfungien
dc.subjectepithelial cellsen
dc.subjectcytokineen
dc.subjectintegrinen
dc.subjectmembrane raftsen
dc.subjectSrc-family kinasesen
dc.titleHistoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitmenten
dc.typeinfo:eu-repo/semantics/article
Arquivos
Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
WOS000374596000001.pdf
Tamanho:
933.27 KB
Formato:
Adobe Portable Document Format
Descrição:
Baixar
Coleções
EPM - Artigos