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Recombinant paracoccin reproduces the biological properties of the native protein and induces protective Th1 immunity against Paracoccidioides brasiliensis infection.

Authors
  • Alegre, Ana Claudia Paiva
  • Oliveira, Aline Ferreira
  • Dos Reis Almeida, Fausto Bruno
  • Roque-Barreira, Maria Cristina
  • Hanna, Ebert Seixas
Type
Published Article
Journal
PLoS Neglected Tropical Diseases
Publisher
Public Library of Science
Publication Date
Apr 01, 2014
Volume
8
Issue
4
Identifiers
DOI: 10.1371/journal.pntd.0002788
PMID: 24743161
Source
Medline
License
Unknown

Abstract

Our results showed that the recombinant protein reproduced the biological properties described for the native protein-including binding to laminin in a manner that is dependent on carbohydrate recognition-showed N-acetylglucosaminidase activity, and stimulated murine peritoneal macrophages to produce high levels of TNF-α and nitric oxide. Considering the immunomodulatory potential of glycan-binding proteins, we also investigated whether prophylactic administration of recombinant paracoccin affected the course of experimental paracoccidioidomycosis in mice. In comparison to animals injected with vehicle (controls), mice treated with recombinant paracoccin displayed lower pulmonary fungal burdens and reduced pulmonary granulomas. These protective effects were associated with augmented pulmonary levels of IL-12 and IFN-γ. We also observed that injection of paracoccin three days before challenge was the most efficient administration protocol, as the induced Th1 immunity was balanced by high levels of pulmonary IL-10, which may prevent the tissue damage caused by exacerbated inflammation. The results indicated that paracoccin is the protein encoded by PADG-3347, and we propose that this gene and homologous proteins in other P. brasiliensis strains be called paracoccin. We also concluded that recombinant paracoccin confers resistance to murine P. brasiliensis infection by exerting immunomodulatory effects.

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