دورية أكاديمية
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Therapeutic administration of recombinant Paracoccin confers protection against paracoccidioides brasiliensis infection: involvement of TLRs.

التفاصيل البيبلوغرافية
العنوان: Therapeutic administration of recombinant Paracoccin confers protection against paracoccidioides brasiliensis infection: involvement of TLRs.
المؤلفون: Alegre-Maller AC; Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil., Mendonça FC; Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil., da Silva TA; Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil., Oliveira AF; Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil., Freitas MS; Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil., Hanna ES; Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil., Almeida IC; Border Biomedical Research Center (BBRC), Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, United States of America., Gay NJ; Department of Biochemistry, Cambridge University, Cambridge, United Kingdom., Roque-Barreira MC; Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil.
المصدر: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2014 Dec 04; Vol. 8 (12), pp. e3317. Date of Electronic Publication: 2014 Dec 04 (Print Publication: 2014).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Fungal Proteins/*administration & dosage , Lectins/*administration & dosage , Paracoccidioidomycosis/*prevention & control , Toll-Like Receptors/*immunology, Animals ; Fungal Proteins/immunology ; HEK293 Cells ; Humans ; Lectins/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Paracoccidioidomycosis/drug therapy ; Paracoccidioidomycosis/immunology ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/immunology
مستخلص: Background: Paracoccin (PCN) is an N-acetylglucosamine-binding lectin from the human pathogenic fungus Paracoccidioides brasiliensis. Recombinant PCN (rPCN) induces a T helper (Th) 1 immune response when prophylactically administered to BALB/c mice, protecting them against subsequent challenge with P. brasiliensis. In this study, we investigated the therapeutic effect of rPCN in experimental paracoccidioidomycosis (PCM) and the mechanism accounting for its beneficial action.
Methodology/principal Findings: Four distinct regimens of rPCN administration were assayed to identify which was the most protective, relative to vehicle administration. In all rPCN-treated mice, pulmonary granulomas were less numerous and more compact. Moreover, fewer colony-forming units were recovered from the lungs of rPCN-treated mice. Although all therapeutic regimens of rPCN were protective, maximal efficacy was obtained with two subcutaneous injections of 0.5 µg rPCN at 3 and 10 days after infection. The rPCN treatment was also associated with higher pulmonary levels of IL-12, IFN-γ, TNF-α, nitric oxide (NO), and IL-10, without IL-4 augmentation. Encouraged by the pulmonary cytokine profile of treated mice and by the fact that in vitro rPCN-stimulated macrophages released high levels of IL-12, we investigated the interaction of rPCN with Toll-like receptors (TLRs). Using a reporter assay in transfected HEK293T cells, we verified that rPCN activated TLR2 and TLR4. The activation occurred independently of TLR2 heterodimerization with TLR1 or TLR6 and did not require the presence of the CD14 or CD36 co-receptors. The interaction between rPCN and TLR2 depended on carbohydrate recognition because it was affected by mutation of the receptor's N-glycosylation sites. The fourth TLR2 N-glycan was especially critical for the rPCN-TLR2 interaction.
Conclusions/significance: Based on our results, we propose that PCN acts as a TLR agonist. PCN binds to N-glycans on TLRs, triggers regulated Th1 immunity, and exerts a therapeutic effect against P. brasiliensis infection.
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معلومات مُعتمدة: United Kingdom Wellcome Trust; 100321 United Kingdom Wellcome Trust; G1000133 United Kingdom MRC_ Medical Research Council; G12 MD007592 United States MD NIMHD NIH HHS
المشرفين على المادة: 0 (Fungal Proteins)
0 (Lectins)
0 (Recombinant Proteins)
0 (Toll-Like Receptors)
0 (paracoccin, Paracoccidioides brasiliensis)
تواريخ الأحداث: Date Created: 20141205 Date Completed: 20160201 Latest Revision: 20220129
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4256291
DOI: 10.1371/journal.pntd.0003317
PMID: 25474158
قاعدة البيانات: MEDLINE
الوصف
تدمد:1935-2735
DOI:10.1371/journal.pntd.0003317