title: Paracoccidioides brasiliensis induces recruitment of α3 and α5 integrins into epithelial cell membrane rafts, leading to cytokine secretion.
abstract: Paracoccidioides brasiliensis is one of the etiological agents of paracoccidioidomycosis, a human systemic mycosis, highly prevalent in Latin America. In the present work, we demonstrate that P. brasiliensis yeasts promote IL-6 and IL-8 secretion by the human lung epithelial cell line A549 in an integrin-dependent manner. In fact, small interfering RNA directed to α3 and α5 integrins decreased IL-6 and IL-8 levels in P. brasiliensis-infected A549 cell cultures. This fungus also led to an increase in the expression of α3 and α5 integrins in this epithelial cell line. In addition, P. brasiliensis yeasts promoted α3 and α5 integrins clustering into A549 cell membrane rafts. Furthermore, epithelial cell membrane raft disruption with nystatin decreased IL-6 and IL-8 levels in P. brasiliensis-A549 cell cultures. Therefore, by increasing host α3 and α5 integrins levels and clustering these receptors into membrane rafts, P. brasiliensis yeasts may modulate host inflammation.
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 862, 6(o) andar, São Paulo, SP, 04023-062, Brazil.
authors.forename: Bianca C S C
authors.initials: BC
authors.lastname: Barros
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 862, 6(o) andar, São Paulo, SP, 04023-062, Brazil.
authors.forename: Paloma K
authors.initials: PK
authors.lastname: Maza
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 862, 6(o) andar, São Paulo, SP, 04023-062, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Alcantara
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 862, 6(o) andar, São Paulo, SP, 04023-062, Brazil. Electronic address: erika.suzuki@unifesp.br.
authors.forename: Erika
authors.initials: E
authors.lastname: Suzuki
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D039422:Integrin alpha3 / Q000378:metabolism*; D039482:Integrin alpha5 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D010228:Paracoccidioides / Q000276:immunology*
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D039422:Integrin alpha3; D039482:Integrin alpha5; D015850:Interleukin-6; D016209:Interleukin-8
keywords: Epithelial cells; Integrins; Interleukin-6; Interleukin-8; Membrane microdomains; Paracoccidioides