title: Immunization with recombinant Pb27 protein reduces the levels of pulmonary fibrosis caused by the inflammatory response against Paracoccidioides brasiliensis.
abstract: Paracoccidioidomycosis (PCM) is a systemic mycosis in which the host response to the infectious agent typically consists of a chronic granulomatous inflammatory process. This condition causes lesions that impair lung function and lead to chronic pulmonary insufficiency resulting from fibrosis development, which is a sequel and disabling feature of the disease. The rPb27 protein has been studied for prophylactic and therapeutic treatment against PCM. Previous studies from our laboratory have shown a protective effect of rPb27 against PCM. However, these studies have not determined whether rPb27 immunization prevents lung fibrosis. We therefore conducted this study to investigate fibrosis resulting from infection by Paracoccidioides brasiliensis in the lungs of animals immunized with rPb27. Animals were immunized with rPb27 and subsequently infected with a virulent strain of P. brasiliensis. Fungal load was evaluated by counting colony-forming units, and Masson's trichrome staining was performed to evaluate fibrosis at 30 and 90 days post-infection. The levels of CCR7, active caspase 3, collagen and cytokines were analyzed. At the two time intervals mentioned, the rPb27 group showed lower levels of fibrosis on histology and reduced levels of collagen and the chemokine receptor CCR7 in the lungs. CCR7 was detected at higher levels in the control groups that developed very high levels of pulmonary fibrosis. Additionally, the immunized groups showed high levels of active caspase 3, IFN-γ, TGF-β and IL-10 in the early phase of P. brasiliensis infection. Immunization with Pb27, in addition to its protective effect, was shown to prevent pulmonary fibrosis.
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Elis Araujo
authors.initials: EA
authors.lastname: Morais
authors.forename: Estefânia Mara do Nascimento
authors.initials: EM
authors.lastname: Martins
authors.forename: Jankerle Neves
authors.initials: JN
authors.lastname: Boelone
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.forename: Alfredo Miranda
authors.initials: AM
authors.lastname: Goes
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D000946:Antigens, Fungal / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D015725:Fluconazole / Q000627:therapeutic use; D005656:Fungal Proteins / Q000008:administration & dosage / Q000276:immunology*; D005657:Fungal Vaccines / Q000276:immunology; D007114:Immunization; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D011425:Propionibacterium acnes / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D054400:Receptors, CCR7 / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D000946:Antigens, Fungal; C515371:Ccr7 protein, mouse; D005656:Fungal Proteins; D005657:Fungal Vaccines; C556062:IL10 protein, mouse; C000606073:Pb27 protein, Paracoccidioides brasiliensis; D054400:Receptors, CCR7; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma; D015725:Fluconazole; D003094:Collagen; D053148:Caspase 3