The importance of Toll-like receptor 4 during experimental Sporothrix brasiliensis infection

Author(s)

Rossato, Luana ^[1] ; dos Santos, Suelen Silvana ^[1] ; Ferreira, Lucas Goncalves ^[1] ; de Almeida, Sandro Rogerio ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Medical Mycology; v. 57, n. 4, p. 489-495, JUN 2019.
• Web of Science Citations: 1

Abstract

Here we investigated the importance of Toll-like receptor 4 (TLR-4) in innate immune response to Sporothrix brasiliensis, a virulent fungus of Sporothrix spp. In vitro assays, using C57Bl/6 (wild type {[}WT]) bone marrow-derived macrophages (BMDMs), and TLR-4 knockout (TLR-4(-/-)) showed that the absence of TLR-4 resulted in impaired phagocytosis and lower levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and nitric oxide. In vivo assays were also performed, and the mice (WT and TLR-4(-/-)) were intraperitoneally infected with S. brasiliensis yeast ATCC MyA-4831 and euthanized on days 7, 14, and 28 postinfection, with the following parameters evaluated: fungal burden in liver, spleen, kidney, and brain, and the production of cytokines interferon gamma (IFN-alpha), TNF-alpha, IL-2, IL-4, IL-6, and IL-10. The results demonstrate the macrophages dependency on TLR-4 for inflammatory activation and in the absence of TLR-4 during experimental S. brasiliensis infection enhanced dissemination occurred after 14 and 28 days. These data show that TLR-4 signals are important for the recognition of S. brasiliensis by macrophages, and their absence promotes the persistence of the infection. (AU)

• FAPESP's process: 13/19213-4 - Study of interaction between macrophages opposite species Sporothrix brasiliensis.
• Grantee: Luana Rossato
• Support Opportunities: Scholarships in Brazil - Doctorate