title: Evaluation of in situ expression of effector and regulatory cytokines, TLR, galectins and matrix metalloproteinases in oral manifestations of paracoccidioidomycosis.
abstract: BACKGROUND
  Although the pathophysiology of paracoccidioidomycosis (PCM) is not completely understood, the study of immune response against fungus has provided insight into understanding the natural course of the disease and its clinical manifestations, hence contributing to the development of preventive measures and treatment proposals. The aim of this study was to evaluate the histopathological and immunological aspects involved in the role of different effector and regulatory responses, as well as the correlation between the TLRs, Galectins, Matrix Metalloproteinases and cytoplasmic proteases of mast cells in this infection.
  
  
  METHODS
  Sixteen biopsy specimens with oral lesions of chronic PCM, as well as 13 sections of normal oral mucosa were analyzed. Histopathological and immunological aspects involved in the role of different effector and regulatory responses were evaluated. Indirect immunohistochemistry was performed for IL-17, IL-10, IL-4, TGF-β, FoxP3, Gal-1, Gal-3, Gal-9, TLR-2, TLR-4, MMP-3 and MMP-9, as well as for chymase and tryptase for mast cells identification. Fibrosis was quantified using Picrosirius.
  
  
  RESULTS
  There was a significant increase in the area of fibrosis and in the number of cells expressing IL-10, IL-4, IL-17, FoxP3, Gal-3, TLR-2, MMP3 and MMP9 in patients with PCM in comparison with patients in the group control. There was no difference in the expression of TGF-β, TLR-4, Gal-1 or Gal-9. Mast cells number was found to be significantly lower in oral chronic PCM when compared to control samples after quantification of mast cells and expression of chymase and tryptase. PCM granulomas were classified to the morphological aspects in organized ou non-organized. Expression of IL-4 in non-organized granulomas was significantly higher.
  
  
  CONCLUSIONS
  The proteins studied herein appear to play an important role in the development and maintenance of oral lesions of PCM, as well as in the processes of development and progression of lesions caused by the fungus and by the immune response associated with the infection.
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, Brazil.
authors.forename: Marcelo Sivieri
authors.initials: MS
authors.lastname: de Araújo
authors.affiliation: Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, Brazil.
authors.forename: Polyanna Miranda
authors.initials: PM
authors.lastname: Alves
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil.
authors.forename: Lilian Margareth Biagioni
authors.initials: LM
authors.lastname: de Lima
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil.
authors.forename: Marcelo Fernandes
authors.initials: MF
authors.lastname: da Silva
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, Brazil.
authors.forename: Sanívia Aparecida
authors.initials: SA
authors.lastname: de Lima Pereira
authors.affiliation: Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, Brazil.
authors.forename: Virmondes
authors.initials: V
authors.lastname: Rodrigues
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, Brazil. Electronic address: denise.rodrigues@uniube.br.
authors.forename: Denise Bertulucci Rocha
authors.initials: DB
authors.lastname: Rodrigues
mesh_terms: D001706:Biopsy; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009059:Mouth Diseases; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D037161:Galectins; D051193:Toll-Like Receptors; D020782:Matrix Metalloproteinases
keywords: Effector cytokines; Galectins; Mast cells peptidases; Matrix metalloproteinases; Oral paracoccidioidomycosis; Regulatory cytokines; Toll-like receptors