Peptidorhamnomannan from Lomentospora prolificans modulates the inflammatory response in macrophages infected with Candida albicans

Author(s)

da Silva Xisto, Mariana Ingrid Dutra ^[1] ; Santos, Suelen S. ^[2] ; Rossato, Luana ^[2] ; Yamada Yoshikawa, Fabio Seiti ^[2] ; Tavares Haido, Rosa Maria ^[3] ; de Almeida, Sandro Rogerio ^[2] ; Barreto-Bergter, Eliana ^[1]

Affiliation

^[1] Univ Fed Rio de Janeiro UFRJ, Dept Microbiol Geral, Lab Quim Biol Microrganismos, Inst Microbiol Paulo de Goes, BR-21941902 Rio De Janeiro, RJ - Brazil

^[2] Fac Ciencias Farmaceut USP, Dept Anal Clin & Toxicol, Sao Paulo - Brazil

^[3] Univ Fed Estado Rio de Janeiro, Dept Microbiol & Parasitol, Inst Biomed, Rio de Janeiro, RJ - Brazil

• Document type: Journal article
• Source: BMC Microbiology; v. 20, n. 1 AUG 6 2020.
• Web of Science Citations: 0

Abstract

BackgroundPeptidorhamnomannan is a glycoconjugate that consists of a peptide chain substituted by O- and N-linked glycans, present on the cell surface of Lomentospora prolificans, a saprophytic fungus which is widely distributed in regions with temperate climates. O-linked oligosaccharides from peptidorhamnomannan isolated from Lomentospora prolificans conidia are recognized by macrophages mediating macrophage - conidia interaction. In this work, peptidorhamnomannan was isolated from L. prolificans mycelium cell wall and its role in macrophage - Candida albicans interaction was evaluated.ResultsPurified peptidorhamnomannan inhibits the reactivity of rabbit immune sera to mycelial and conidia forms of L. prolificans, indicating that this glycoconjugate is exposed on the fungal surface and can mediate interaction with host immune cells. We demonstrated that peptidorhamnomannan leads to TNF-alpha production in J774 macrophages for 1, 2 and 3h of incubation, suggesting that this glycoconjugate may have a beneficial role in the response to fungal infections. In order to confirm this possibility, the effect of peptidorhamnomannan on the macrophage - C. albicans interaction was evaluated. Macrophages treated with peptidorhamnomannan led to a lower fungal survival, suggesting that peptidorhamnomannan induces an increased fungicidal activity in macrophages. Furthermore, TNF-alpha levels were measured in supernatants after macrophage - C. albicans interaction for 1, 2 and 3h. Peptidorhamnomannan treatment led to a higher TNF-alpha production at the beginning of the interaction. However, the release of TNF-alpha was not maintained after 1h of incubation. Besides, peptidorhamnomannan did not show any inhibitory or fungicidal effect in C. albicans when used at 100 mu g/ml but it was able to kill C. albicans at a concentration of 400 mu g/ml.ConclusionWe suggest that peptidorhamnomannan acts as a molecular pattern on the invading pathogen, promotes TNF-alpha production and, thus, increases macrophage fungicidal activity against Candida albicans. (AU)

• FAPESP's process: 16/04729-3 - Bases of cellular immune response in chromoblastomycosis and sporotrichosis: implications for vaccine therapy
• Grantee: Sandro Rogerio de Almeida
• Support Opportunities: Research Projects - Thematic Grants