title: M2 macrophages and inflammatory cells in oral lesions of chronic paracoccidioidomycosis.
abstract: BACKGROUND
  Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides brasiliensis (Pb) and associated with deficient cellular immune response, which is modulated by inflammatory cells, mainly macrophages, and cytokines. Recently, the comprehension of the macrophage polarization mediated by Th1 and Th2 cytokines has contributed to elucidate the immune response that takes part in some diseases. Thus, the aim of this study was to assess the presence of Th1- and Th2-immune response and also Pb counting in oral lesions of chronic PCM.
  
  
  METHODS
  Forty-eight cases of chronic PCM oral lesions were included. All cases were classified as loose or dense granulomas. S100 protein, IL-1β, IL-6, TNF-α, CD163 and CD68 immunoexpressions, and Pb localization were evaluated. The fungi present in the tissue were quantified by anti-Pb antibody.
  
  
  RESULTS
  Most patients were white men with mean age of 47 years old and showed higher incidence of multiple lesions. Loose granulomas were predominant and exhibited a great amount of M2 macrophages, which were visualized with anti-CD163 antibody. The expression for CD163 and CD68 was similar (P = 0.05), highlighting the predominance of M2 macrophages in PCM. IL-1β, IL-6, and TNF-α immunoexpression did not significantly change with CD163, CD68, and S100 protein. The number of fungi was significantly higher in cases with intense IL-1β immunoexpression (P = 0.003).
  
  
  CONCLUSIONS
  M2-activated macrophages were the majority among inflammatory cells in chronic PCM, characterizing the action of a Th2-immune response. Nevertheless, Th1 cytokines were also found; mainly IL-1β, which was associated with fungi counting in oral lesions.
authors.affiliation: Department of Clinic and Surgery, School of Dentistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
authors.forename: Marina Lara
authors.initials: ML
authors.lastname: de Carli
authors.affiliation: Department of Clinic and Surgery, School of Dentistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
authors.forename: Marta
authors.initials: M
authors.lastname: Miyazawa
authors.affiliation: Pathology Center, Adolfo Lutz Institute, São Paulo, São Paulo, Brazil.
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.affiliation: Pathology Center, Adolfo Lutz Institute, São Paulo, São Paulo, Brazil.
authors.forename: Neuza Kasumi
authors.initials: NK
authors.lastname: Shirata
authors.affiliation: Department of Stomatology- Area of Pathology, Bauru Dental School, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Denise Tostes
authors.initials: DT
authors.lastname: Oliveira
authors.affiliation: Department of Clinic and Surgery, School of Dentistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
authors.forename: Alessandro Antônio Costa
authors.initials: AA
authors.lastname: Pereira
authors.affiliation: Department of Clinic and Surgery, School of Dentistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
authors.forename: João Adolfo Costa
authors.initials: JA
authors.lastname: Hanemann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009059:Mouth Diseases / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011956:Receptors, Cell Surface / Q000276:immunology; D009418:S100 Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D009418:S100 Proteins; D014409:Tumor Necrosis Factor-alpha; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Paracoccidioides; inflammation; macrophages; paracoccidioidomycosis