resumo
Systemic fungal infections are associated with significant morbidity and mortality, and Candida albicans is the most common causative agent. Recognition of yeast cells by immune cell surface receptors can trigger phagocytosis of fungal pathogens and a pro-inflammatory response that may contribute to fungal elimination. Nevertheless, the elicited inflammatory response may be deleterious to the host by causing excessive tissue damage. We developed a nanoparticle-based approach to modulate the host deleterious inflammatory consequences of fungal infection by using beta 1,3-glucan-functionalized polystyrene (beta-Glc-PS) nanoparticles. beta-Glc-PS nanoparticles decreased the levels of the proinflammatory cytokines TNF-alpha, IL-6, IL-1 beta and IL-12p40 detected in in vitro culture supernatants of bone marrow-derived dendritic cells and macrophage challenged with C. albicans cells. Moreover, beta-Glc-PS nanoparticles impaired the production of reactive oxygen species by bone marrow-derived dendritic cells incubated with C. albicans. This immunomodulatory effect was dependent on the nanoparticle size. Overall, beta-Glc-PS nanoparticles reduced the proinflammatory response elicited by fungal cells in mononuclear phagocytes, setting the basis for a targeted therapy aimed at protecting the host by lowering the inflammatory cost of infection.
palavras-chave
YEAST PHAGOCYTOSIS; PROTEIN ADSORPTION; CELL-WALL; POLYSACCHARIDES; INFECTION; SIZE; RECOGNITION; MECHANISMS; CURVATURE; PARTICLES
categoria
Chemistry; Science & Technology - Other Topics; Materials Science; Physics
autores
Lima, T; Gunnarsson, SB; Coelho, E; Evtuguin, DV; Correia, A; Coimbra, MA; Cedervall, T; Vilanova, M
nossos autores
Dmitry Evtyugin
Professor Associado com Agregação
Elisabete Verde Martins Coelho
Bolseiro de pós-Doutoramentoagradecimentos
y This work received financial support from PT national funds (FCT/MCTES, Fundacao para a Ciencia e Tecnologia and Ministerio da Ciencia, Tecnologia e Ensino Superior). LAQV/REQUIMTE (UIDB/50006/2020, UIDP/50006/2020), through national founds and, where applicable, co-funded by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). T.L. was supported by FCT PhD grant (PD/BD/128393/2017) from BiotechHealth International Doctoral programme. A.C. was supported by FCT Individual CEEC (CEEC IND/01514/2017). E.C. was supported by FCT through program DL 57/2016-Norma transitoria (CDL-CTTRI-88-ARH/2018-REF.049-88-ARH/2018).