Paracoccidioides brasiliensis downmodulates alpha 3 integrin levels in human lung epithelial cells in a TLR2-dependent manner

Autor(es)

Silva Campitelli de Barros, Bianca Carla ^[1] ; Almeida, Bruna Rocha ^[1] ; Suzuki, Erika ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, BR-04023062 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 NOV 10 2020.
• Citações Web of Science: 0

Resumo

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and may be caused by the species Paracoccidioides brasiliensis. In the lungs, this fungus interacts with epithelial cells, activating host cell signalling pathways, resulting in the production of inflammatory mediators. This event may be initiated through the activation of Pattern-Recognition Receptors such as Toll-like Receptors (TLRs). By interacting with cell wall components, TLR2 is frequently related to fungal infections. In this work, we show that, after 24 h post-infection with P. brasiliensis, A549 lung epithelial cells presented higher TLR2 levels, which is important for IL-8 secretion. Besides, integrins may also participate in pathogen recognition by host cells. We verified that P. brasiliensis increased alpha 3 integrin levels in A549 cells after 5 h of infection and promoted interaction between this receptor and TLR2. However, after 24 h, surprisingly, we verified a decrease of alpha 3 integrin levels, which was dependent on direct contact between fungi and epithelial cells. Likewise, we observed that TLR2 is important to downmodulate alpha 3 integrin levels after 24 h of infection. Thus, P. brasiliensis can modulate the host inflammatory response by exploiting host cell receptors and cell signalling pathways. (AU)

• Processo FAPESP: 19/26693-9 - Modulação de mecanismos celulares por Paracoccidioides em células epiteliais pulmonares
• Beneficiário: Erika Suzuki de Toledo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/06285-5 - Envolvimento de receptores do tipo Toll, integrinas e suas respectivas vias de sinalização celular na secreção de citocinas por células epiteliais durante a infecção com Paracoccidioides brasiliensis
• Beneficiário: Bianca Carla Silva Campitelli de Barros
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/25652-6 - Estudo da comunicação entre receptores e suas vias de sinalização na secreção de citocinas, induzida por fungos em células epiteliais
• Beneficiário: Erika Suzuki de Toledo
• Modalidade de apoio: Auxílio à Pesquisa - Regular