title: Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected with Paracoccidioides brasiliensis.
abstract: Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 10(6) or 2 × 10(6) P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with 1.5 × 10(6) yeast cells died during the first two weeks after infection. When mice were treated and infected with 2 × 10(6) yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γ and IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis.
authors.affiliation: Medical and Experimental Mycology Unit, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.
authors.forename: Paula Andrea
authors.identifier: 0000-0001-7983-1293
authors.initials: PA
authors.lastname: Pino-Tamayo
authors.affiliation: Medical and Experimental Mycology Unit, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.
authors.forename: Juan David
authors.identifier: 0000-0001-6000-2348
authors.initials: JD
authors.lastname: Puerta-Arias
authors.affiliation: Medical and Experimental Mycology Unit, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.
authors.forename: Damaris
authors.initials: D
authors.lastname: Lopera
authors.affiliation: Medical and Experimental Mycology Unit, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.
authors.forename: Martha Eugenia
authors.initials: ME
authors.lastname: Urán-Jiménez
authors.affiliation: Basic and Applied Microbiology Research Group (MICROBA), School of Microbiology, Universidad de Antioquia, Calle 70 No. 52-21, Medellín, Colombia.
authors.forename: Ángel
authors.identifier: 0000-0002-7052-7938
authors.initials: Á
authors.lastname: González
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008171:Lung Diseases / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000002:abnormalities; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010228:Paracoccidioides / Q000276:immunology* / Q000472:pathogenicity*; D010229:Paracoccidioidomycosis / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018925:Chemokines; D016207:Cytokines