title: TLR 9 involvement in early protection induced by immunization with rPb27 against Paracoccidioidomycosis.
abstract: Paracoccidioidomycosis is caused by fungi of the Paracoccidioides genus and constitutes the most prevalent deep mycosis in Latin America. Toll-like receptors promote immune response against infectious agents. Recently, it was reported that TLR9 is crucial for mice survival during the first 48 h of P. brasiliensis infection. In this study, we used CPG oligodeoxynucleotide motif as an adjuvant with and without rPb27 to immunize mice against Paracoccidioidomycosis. CPG adjuvant induced differential recruitment of lymphocytes in the inflammatory process and a lower recruitment of neutrophils. In addition, CPG induced the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IL-6 and IL-12; increased phagocytic ability and microbicidal activity by macrophages; and induced differential production of lgG2a and lgG2b, subtypes of Ig. Knockout mice for TLR9 and IL-12 showed higher fungal loads and rates of mortality compared to control mice after 30 days of infection. The association between CPG and rPb27 induced a high level of protection against Paracoccidioidomycosis after the first 30 days of infection but not at 60 days. Our findings demonstrate that TLR 9 plays a role in the protection induced by immunization with rPb27 and confirms the importance of TLR9 in the initial protection against Paracoccidioidomycosis.
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.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Daniela Ferreira
authors.initials: DF
authors.lastname: Chame
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Eliza Mathias
authors.initials: EM
authors.lastname: Melo
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Junnia Alvarenga
authors.initials: JA
authors.lastname: de Carvalho Oliveira
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Ana Cláudia Chagas
authors.initials: AC
authors.lastname: de Paula
authors.affiliation: Laboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Andiara Cardoso
authors.initials: AC
authors.lastname: Peixoto
authors.affiliation: Service de Médecine Tropicale et Humanitaire, Université de Genève, Switzerland.
authors.forename: Lílian
authors.initials: L
authors.lastname: da Silva Santos
authors.affiliation: Service de Médecine Tropicale et Humanitaire, Université de Genève, Switzerland.
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: Laboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Remo Castro
authors.initials: RC
authors.lastname: Russo
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. Electronic address: alfredomgoes@gmail.com.
authors.forename: Alfredo Miranda
authors.initials: AM
authors.lastname: de Goes
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015169:Colony Count, Microbial; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology*; D007843:Latin America; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D005656:Fungal Proteins; D009838:Oligodeoxyribonucleotides; C000606073:Pb27 protein, Paracoccidioides brasiliensis; D011994:Recombinant Proteins; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D014614:Vaccines, Synthetic
keywords: Adjuvant; CPG; Paracoccidioides brasiliensis; Paracoccidioidomycosis; RPB27; TLR9