PMID- 31770592 OWN - NLM STAT- MEDLINE DCOM- 20201106 LR - 20201106 IS - 1769-714X (Electronic) IS - 1286-4579 (Linking) VI - 22 IP - 3 DP - 2020 Apr TI - Enhanced expression of NLRP3 inflammasome components by monocytes of patients with pulmonary paracoccidioidomycosis is associated with smoking and intracellular hypoxemia. PG - 137-143 LID - S1286-4579(19)30165-0 [pii] LID - 10.1016/j.micinf.2019.11.001 [doi] AB - Paracoccidioidomycosis (PCM) is a systemic mycosis caused by thermally dimorphic fungi of the genus Paracoccidioides that affects predominantly 30-60-year-old male rural workers. The main clinical forms of the disease are acute/subacute, chronic (CF); almost all CF patients develop pulmonary fibrosis, and they also exhibit emphysema due to smoke. An important cytokine in this context, IL-1beta, different from the others, is produced by an intracellular multimolecular complex called inflammasome that is activated by pathogens and/or host signs of damage. Inflammasome has been recognized for its contribution to chronic inflammatory diseases, from that, we hypothesized that this activation could be involved in paracoccidioidomycosis, contributing to chronic inflammation. While inflammasome activation has been demonstrated in experimental models of Paracoccidioides brasiliensis infection, no information is available in patients, leading us to investigate the participation of NLRP3-inflammasome machinery in CF/PCM patients from a Brazilian endemic area. Our findings showed increased priming in mRNA levels of NLRP3 inflammasome genes by monocytes of PCM patients in vitro than healthy controls. Similar intracellular protein expression of NLRP3, CASP-1, ASC, and IL-1beta were also observed in freshly isolated monocytes of PCM patients and smoker controls. Increased expression of NLRP3 and ASC was observed in monocytes from PCM patients under hypoxia in comparison with smoker controls. For the first time, we showed that primed monocytes of CF-PCM patients were associated with enhanced expression of components of NLRP3-inflammasome due to smoke. Also, hypoxemia boosted this machinery. These findings reinforce the systemic low-grade inflammation activation observed in PCM during and after treatment. CI - Copyright (c) 2019 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. FAU - Amorim, Barbara Casella AU - Amorim BC AD - Sao Paulo State University (UNESP), School of Sciences, Bauru, SP, Brazil; Sao Paulo State University (UNESP), Medical School, Botucatu, SP, Brazil. FAU - Pereira-Latini, Ana Carla AU - Pereira-Latini AC AD - Lauro de Souza Lima Institute, Bauru, SP, Brazil. FAU - Golim, Marjorie de Assis AU - Golim MA AD - Sao Paulo State University (UNESP), Medical School, Botucatu, SP, Brazil. FAU - Ruiz Junior, Raul Lopes AU - Ruiz Junior RL AD - Sao Paulo State University (UNESP), Medical School, Botucatu, SP, Brazil. FAU - Yoo, Hugo Hyung Bok AU - Yoo HHB AD - Sao Paulo State University (UNESP), Medical School, Botucatu, SP, Brazil. FAU - Arruda, Maria Sueli Parreira de AU - Arruda MSP AD - Sao Paulo State University (UNESP), School of Sciences, Bauru, SP, Brazil. FAU - Tavares, Aldo Henrique AU - Tavares AH AD - University of Brasilia (UnB), Institute of Biological Sciences Brasilia, Federal District, Brazil. FAU - Cavalcante, Ricardo de Souza AU - Cavalcante RS AD - Sao Paulo State University (UNESP), Medical School, Botucatu, SP, Brazil. FAU - Mendes, Rinaldo Poncio AU - Mendes RP AD - Sao Paulo State University (UNESP), Medical School, Botucatu, SP, Brazil. FAU - Pontillo, Alessandra AU - Pontillo A AD - University of Sao Paulo (USP), Institute of Biomedical Sciences, SP, Brazil. FAU - Venturini, James AU - Venturini J AD - Sao Paulo State University (UNESP), Medical School, Botucatu, SP, Brazil; Federal University of Mato Grosso do Sul (UFMS), Medical School, Campo Grande, MS, Brazil. Electronic address: james.venturini@ufms.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191123 PL - France TA - Microbes Infect JT - Microbes and infection JID - 100883508 RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLRP3 protein, human) SB - IM MH - Cell Hypoxia MH - Humans MH - Invasive Fungal Infections/immunology/microbiology MH - Lung Diseases, Fungal/microbiology MH - Monocytes/*immunology/microbiology MH - NLR Family, Pyrin Domain-Containing 3 Protein/*genetics/immunology MH - Paracoccidioides MH - Paracoccidioidomycosis/*immunology/microbiology MH - Pulmonary Fibrosis/immunology/microbiology MH - *Smoking OTO - NOTNLM OT - Antifungal therapy OT - Hypoxia OT - Inflammasome OT - Monocytes OT - Paracoccidioidomycosis OT - Pulmonary fibrosis COIS- Declaration of Competing Interest We declare that the manuscript does not present any potential conflicts of interest. EDAT- 2019/11/27 06:00 MHDA- 2020/11/11 06:00 CRDT- 2019/11/27 06:00 PHST- 2019/07/05 00:00 [received] PHST- 2019/11/14 00:00 [revised] PHST- 2019/11/15 00:00 [accepted] PHST- 2019/11/27 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2019/11/27 06:00 [entrez] AID - S1286-4579(19)30165-0 [pii] AID - 10.1016/j.micinf.2019.11.001 [doi] PST - ppublish SO - Microbes Infect. 2020 Apr;22(3):137-143. doi: 10.1016/j.micinf.2019.11.001. Epub 2019 Nov 23.