title: Paracoccidioides brasiliensis GP43-derived peptides are potent modulators of local and systemic inflammatory response.
abstract: Paracoccidioidomycosis is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. Its major antigen is a 43 kDa glycoprotein whose peptides embody different functions: P10 peptide, a T-cell epitope, induces protective response while P4 and P23 peptides inhibit both, macrophage functions and inflammatory reaction, thus facilitating infection. Here we investigated the modulating mechanisms of the immune response exerted by P4 and P23 involved in the latter inhibitory effect on macrophages. Moreover we analyzed the peptides effects in different models in vivo. While evaluating whether P4 and P23 present systemic anti-inflammatory effects in vivo, we showed that their intraperitonial administration decreased footpad swelling in mice infected with either P. brasiliensis or Mycobacterium bovis. Both, qPCR and ELISA assays suggested that this anti-inflammatory effect depended on alterations in the kinetics of production of innate immunity modulators such as TNF-α, IL6, IL10 and TLR2. IL10 seems to be early produced than TNF-α and IL6, produced later in presence of peptides. Higher doses or intravenously given P4 and P23 resulted in earlier and more prolonged anti-inflammatory effects. Moreover, continuous treatment with P4 and P23 sustained the anti-inflammatory activity throughout.
authors.affiliation: Universidade Federal de São Paulo - UNIFESP, Department of Microbiology, Immunology and Parasitology, Discipline of Immunology, São Paulo, Brazil.
authors.forename: Fabiana T C
authors.initials: FT
authors.lastname: Konno
authors.forename: Juliana
authors.initials: J
authors.lastname: Maricato
authors.forename: Adriana Y C
authors.initials: AY
authors.lastname: Konno
authors.forename: Márcia G
authors.initials: MG
authors.lastname: Guereschi
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Vivanco
authors.forename: Luciano dos Santos
authors.initials: Ldos S
authors.lastname: Feitosa
authors.forename: Mário
authors.initials: M
authors.lastname: Mariano
authors.forename: José Daniel
authors.initials: JD
authors.lastname: Lopes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000737:chemistry*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005528:Foot / Q000382:microbiology; D005656:Fungal Proteins / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010228:Paracoccidioides / Q000187:drug effects / Q000472:pathogenicity*; D010229:Paracoccidioidomycosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C103180:43 kDa protein, Paracoccidioides; D000893:Anti-Inflammatory Agents; D000946:Antigens, Fungal; D016207:Cytokines; D005656:Fungal Proteins; D006023:Glycoproteins; D010455:Peptides