PMID- 26327485 OWN - NLM STAT- MEDLINE DCOM- 20160329 LR - 20190202 IS - 1935-2735 (Electronic) IS - 1935-2727 (Print) IS - 1935-2727 (Linking) VI - 9 IP - 9 DP - 2015 TI - Neutrophil Extracellular Traps Identification in Tegumentary Lesions of Patients with Paracoccidioidomycosis and Different Patterns of NETs Generation In Vitro. PG - e0004037 LID - 10.1371/journal.pntd.0004037 [doi] LID - e0004037 AB - Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil. It is caused by the thermo-dimorphic fungus of the genus Paracoccidioides (Paracoccidioides brasiliensis and Paracoccidioides lutzii). Innate immune response plays a crucial role in host defense against fungal infections, and neutrophils (PMNs) are able to combat microorganisms with three different mechanisms: phagocytosis, secretion of granular proteins, which have antimicrobial properties, and the most recent described mechanism called NETosis. This new process is characterized by the release of net-like structures called Neutrophil Extracellular Traps (NETs), which is composed of nuclear (decondensed DNA and histones) and granular material such as elastase. Several microorganisms have the ability of inducing NETs formation, including gram-positive and gram-negative bacteria, viruses and some fungi. We proposed to identify NETs in tegumentary lesions of patients with PCM and to analyze the interaction between two strains of P. brasiliensis and human PMNs by NETs formation in vitro. In this context, the presence of NETs in vivo was evidenced in tegumentary lesions of patients with PCM by confocal spectrum analyzer. Furthermore, we showed that the high virulent P. brasiliensis strain 18 (Pb18) and the lower virulent strain Pb265 are able to induce different patterns of NETs formation in vitro. The quantification of extracellular DNA corroborates the idea of the ability of P. brasiliensis in inducing NETs release. In conclusion, our data show for the first time the identification of NETs in lesions of patients with PCM and demonstrate distinct patterns of NETs in cultures challenged with fungi in vitro. The presence of NETs components both in vivo and in vitro open new possibilities for the detailed investigation of immunity in PCM. FAU - Della Coletta, Amanda Manoel AU - Della Coletta AM AD - Department of Pathology, UNESP - Sao Paulo State University, Botucatu Medical School, Botucatu, Sao Paulo, Brazil. FAU - Bachiega, Tatiana Fernanda AU - Bachiega TF AD - Department of Microbiology and Immunology, UNESP-Sao Paulo State University, Biosciences Institute, Botucatu, Sao Paulo, Brazil. FAU - de Quaglia e Silva, Juliana Carvalho AU - de Quaglia e Silva JC AD - Department of Pathology, UNESP - Sao Paulo State University, Botucatu Medical School, Botucatu, Sao Paulo, Brazil. FAU - Soares, Angela Maria Victoriano de Campos AU - Soares AM AD - Department of Microbiology and Immunology, UNESP-Sao Paulo State University, Biosciences Institute, Botucatu, Sao Paulo, Brazil. FAU - De Faveri, Julio AU - De Faveri J AD - Department of Pathology, UNESP - Sao Paulo State University, Botucatu Medical School, Botucatu, Sao Paulo, Brazil. FAU - Marques, Silvio Alencar AU - Marques SA AD - Department of Dermatology and Radiotherapy, UNESP - Sao Paulo State University, Botucatu Medical School, Botucatu, Sao Paulo, Brazil. FAU - Marques, Mariangela Esther Alencar AU - Marques ME AD - Department of Pathology, UNESP - Sao Paulo State University, Botucatu Medical School, Botucatu, Sao Paulo, Brazil. FAU - Ximenes, Valdecir Farias AU - Ximenes VF AD - Department of Chemistry, UNESP-Sao Paulo State University, School of Sciences, Bauru, Sao Paulo, Brazil. FAU - Dias-Melicio, Luciane Alarcao AU - Dias-Melicio LA AD - Department of Pathology, UNESP - Sao Paulo State University, Botucatu Medical School, Botucatu, Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150901 PL - United States TA - PLoS Negl Trop Dis JT - PLoS neglected tropical diseases JID - 101291488 SB - IM MH - Aged MH - Brazil MH - Extracellular Traps/*metabolism MH - Humans MH - Male MH - Microscopy, Confocal MH - Middle Aged MH - Neutrophils/*immunology MH - Paracoccidioides/*immunology MH - Paracoccidioidomycosis/immunology/*pathology MH - Prospective Studies MH - Spectrum Analysis PMC - PMC4556621 COIS- The authors have declared that no competing interests exist. EDAT- 2015/09/04 06:00 MHDA- 2016/03/30 06:00 PMCR- 2015/09/01 CRDT- 2015/09/02 06:00 PHST- 2015/02/04 00:00 [received] PHST- 2015/08/05 00:00 [accepted] PHST- 2015/09/02 06:00 [entrez] PHST- 2015/09/04 06:00 [pubmed] PHST- 2016/03/30 06:00 [medline] PHST- 2015/09/01 00:00 [pmc-release] AID - PNTD-D-15-00181 [pii] AID - 10.1371/journal.pntd.0004037 [doi] PST - epublish SO - PLoS Negl Trop Dis. 2015 Sep 1;9(9):e0004037. doi: 10.1371/journal.pntd.0004037. eCollection 2015.