PMID- 30085101 OWN - NLM STAT- MEDLINE DCOM- 20190429 LR - 20190429 IS - 1460-2709 (Electronic) IS - 1369-3786 (Linking) VI - 57 IP - 4 DP - 2019 Jun 1 TI - The importance of Toll-like receptor 4 during experimental Sporothrix brasiliensis infection. PG - 489-495 LID - 10.1093/mmy/myy048 [doi] AB - 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-gamma), 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. CI - (c) The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. FAU - Rossato, Luana AU - Rossato L AD - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Santos, Suelen Silvana Dos AU - Santos SSD AD - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Ferreira, Lucas Goncalves AU - Ferreira LG AD - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - de Almeida, Sandro Rogerio AU - de Almeida SR AD - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo, Brazil. LA - eng PT - Journal Article PL - England TA - Med Mycol JT - Medical mycology JID - 9815835 RN - 0 (Cytokines) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Animal Structures/microbiology/pathology MH - Animals MH - Cells, Cultured MH - Colony Count, Microbial MH - Cytokines/metabolism MH - Disease Models, Animal MH - *Immunity, Innate MH - Macrophages/immunology/microbiology MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Models, Biological MH - Phagocytosis MH - Sporothrix/*immunology MH - Sporotrichosis/*immunology MH - Toll-Like Receptor 4/*metabolism OTO - NOTNLM OT - Sporothrix brasiliensis OT - BMDMs OT - Toll-like receptor 4 EDAT- 2018/08/08 06:00 MHDA- 2019/04/30 06:00 CRDT- 2018/08/08 06:00 PHST- 2017/12/07 00:00 [received] PHST- 2018/05/21 00:00 [revised] PHST- 2018/06/27 00:00 [accepted] PHST- 2018/08/08 06:00 [pubmed] PHST- 2019/04/30 06:00 [medline] PHST- 2018/08/08 06:00 [entrez] AID - 5063414 [pii] AID - 10.1093/mmy/myy048 [doi] PST - ppublish SO - Med Mycol. 2019 Jun 1;57(4):489-495. doi: 10.1093/mmy/myy048.