title: The combined use of Paracoccidioides brasiliensis Pb40 and Pb27 recombinant proteins enhances chemotherapy effects in experimental paracoccidioidomycosis.
abstract: Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM), a chronic granulomatous mycosis prevalent in Latin America, and cell-mediated immunity represents the main mode of protection against this fungal infection. The conventional treatment for this mycosis involves long periods of therapy resulting in sequels and a high frequency of relapse. The search for new alternative methods of treatment is thus necessary. With this aim, the objective of this work was to evaluate the potential of rPb27 and rPb40 immunization to reduce treatment length and the frequency of relapse when used as an adjuvant to fluconazole chemotherapy in experimental PCM. Combined treatment with the drug and the two proteins reduced CFUs in the lung, liver and spleen to undetectable levels and largely preserved the tissue structure of these organs. At the same time, IFN-γ and TNF-α levels were higher in mice treated as described above than in infected-only mice, while very low production of IL-10 and TGF-β was observed in this treated group. Thus, the combined treatment, using immunization with the two recombinant proteins in addition to fluconazole chemotherapy, showed an additive protective effect after intratracheal challenge. These results provide new prospects for immunotherapy as a treatment for PCM.
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, ICB, Q4-167 zip code 31.270-901, Belo Horizonte, Minas Gerais, Brazil. cfernandes.viviane@gmail.com
authors: Viviane C
authors: VC
authors: Fernandes
authors: Estefânia M N
authors: EM
authors: Martins
authors: Jankerle N
authors: JN
authors: Boeloni
authors: Juliana B
authors: JB
authors: Coitinho
authors: Rogéria
authors: R
authors: Serakides
authors: Alfredo M
authors: AM
authors: Goes
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000946:Antigens, Fungal / Q000235:genetics / Q000276:immunology; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000235:genetics / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: C103540:27 kDa protein, Paracoccidioides brasiliensis; D000276:Adjuvants, Immunologic; D000935:Antifungal Agents; D000946:Antigens, Fungal; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D005656:Fungal Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D015725:Fluconazole