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

Author(s)

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

Affiliation

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

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 NOV 10 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 19/26693-9 - Modulation of the pulmonary epithelial cell mechanisms by Paracoccidioides
• Grantee: Erika Suzuki de Toledo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/06285-5 - Involvement of toll-like receptor, integrins and their respective cell signaling pathways in cytokine secretion by epithelial cells during infection with Paracoccidioides brasiliensis
• Grantee: Bianca Carla Silva Campitelli de Barros
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/25652-6 - Study of the communication between receptors, and their signaling pathways, in fungus-induced cytokine secretion in epithelial cells
• Grantee: Erika Suzuki de Toledo
• Support Opportunities: Regular Research Grants