title: Interleukin 32γ (IL-32γ) is highly expressed in cutaneous and mucosal lesions of American Tegumentary Leishmaniasis patients: association with tumor necrosis factor (TNF) and IL-10.
abstract: BACKGROUND
  The interleukin 32 (IL-32) is a proinflammatory cytokine produced by immune and non-immune cells. It can be induced during bacterial and viral infections, but its production was never investigated in protozoan infections. American Tegumentary Leishmaniasis (ATL) is caused by Leishmania protozoan leading to cutaneous, nasal or oral lesions. The aim of this study was to evaluate the expression of IL-32 in cutaneous and mucosal lesions as well as in peripheral blood mononuclear cells (PBMC) exposed to Leishmania (Viannia) braziliensis.
  
  
  METHODS
  IL-32, tumour necrosis factor (TNF) and IL-10 protein expression was evaluated by immunohistochemistry in cutaneous, mucosal lesions and compared to healthy specimens. The isoforms of IL-32α, β, δ, γ mRNA, TNF mRNA and IL-10 mRNA were assessed by qPCR in tissue biopsies of lesions and healthy skin and mucosa. In addition, PBMC from healthy donors were cultured with amastigotes of L. (V.) braziliensis. In lesions, the parasite subgenus was identified by PCR-RFLP.
  
  
  RESULTS
  We showed that the mRNA expression of IL-32, in particular IL-32γ was similarly up-regulated in lesions of cutaneous (CL) or mucosal (ML) leishmaniasis patients. IL-32 protein was produced by epithelial, endothelial, mononuclear cells and giant cells. The IL-32 protein expression was associated with TNF in ML but not in CL. IL-32 was not associated with IL-10 in both CL and ML. Expression of TNF mRNA was higher in ML than in CL lesions, however levels of IL-10 mRNA were similar in both clinical forms. In all lesions in which the parasite was detected, L. (Viannia) subgenus was identified. Interestingly, L. (V.) braziliensis induced only IL-32γ mRNA expression in PBMC from healthy individuals.
  
  
  CONCLUSIONS
  These data suggest that IL-32 plays a major role in the inflammatory process caused by L. (Viannia) sp or that IL-32 is crucial for controlling the L. (Viannia) sp infection.
authors.forename: Hélio
authors.initials: H
authors.lastname: Galdino
authors.forename: Anetícia Eduarda
authors.initials: AE
authors.lastname: Maldaner
authors.forename: Lívia Lara
authors.initials: LL
authors.lastname: Pessoni
authors.forename: Frederico M
authors.initials: FM
authors.lastname: Soriani
authors.forename: Ledice Inácia de Araújo
authors.initials: LI
authors.lastname: Pereira
authors.forename: Sebastião Alves
authors.initials: SA
authors.lastname: Pinto
authors.forename: Fernanda Bugalho
authors.initials: FB
authors.lastname: Duarte
authors.forename: Clayson Moura
authors.initials: CM
authors.lastname: Gomes
authors.forename: Anna Karoline Aguiar
authors.initials: AK
authors.lastname: Fleuri
authors.forename: Miriam Leandro
authors.initials: ML
authors.lastname: Dorta
authors.forename: Milton Adriano Pelli
authors.initials: MA
authors.lastname: de Oliveira
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Aline Carvalho
authors.initials: AC
authors.lastname: Batista
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Leda Quercia
authors.initials: LQ
authors.lastname: Vieira
authors.affiliation: Institute of Tropical Pathology and Public Healthy, Universidade Federal de Goiás, Rua 235 S/N - Setor Universitário, Goiânia 74605-050, Goiás, Brazil. fatimardias@gmail.com.
authors.forename: Fátima
authors.initials: F
authors.lastname: Ribeiro-Dias
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C496971:IL32 protein, human; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10