title: American tegumentary leishmaniasis: mRNA expression for Th1 and Treg mediators are predominant in patients with recent active disease.
abstract: Besides the Th1×Th2 paradigm, Treg and Th17 cytokines may play a role in the response to American tegumentary leishmaniasis. Considering the sensitivity and accuracy of qPCR and the lack of studies using this approach, we evaluated mRNA expression for IFN-γ, TNF-α, IL-4, IL-10, IL-6, IL-17A, IL-22, TGF-β, Foxp3 and RORC in peripheral blood mononuclear cells (PBMC) from patients with active disease, after stimulation with L. (V.) braziliensis soluble or insoluble fractions. Our results show that the antigens promoted specific mRNA expression related to the immune response in patients with ATL, and the insoluble fraction seems to stimulate the immune response in a higher intensity. The pro-inflammatory response was also fueled by IFN-γ and TNF-α, probably due to the active disease. IL-4, in certain way, seems to regulate this response along with IL-10 that may be produced by Treg cells, which are supposedly present in the patients' samples due the evidenced expression of Foxp3, in the presence of AgIns. In contrast, down-regulated RORC suggests that the significant levels of IL-6 expressed in response to AgSol were not able to induce an expressive Th17 profile along with TGF-β, which might have predominantly contributed to the development of a regulatory profile in the active disease.
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: marinaasouza@gmail.com.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Souza
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: thaysmdealmeida@gmail.com.
authors.forename: Thays M
authors.initials: TM
authors.lastname: Almeida
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: carolina.brelaz@gmail.com.
authors.forename: Maria Carolina A B
authors.initials: MC
authors.lastname: Castro
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: andresadeolinda@gmail.com.
authors.forename: Andresa P
authors.initials: AP
authors.lastname: Oliveira-Mendes
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: amanda.ferreira@gmail.com.
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Almeida
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: oliveira.cbeatriz@gmail.com.
authors.forename: Beatriz C
authors.initials: BC
authors.lastname: Oliveira
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: lf.rocha7@gmail.com.
authors.forename: Lucas F
authors.initials: LF
authors.lastname: Rocha
authors.affiliation: Hospital Universitário Oswaldo Cruz, Universidade de Pernambuco (HUOC/UPE), Brazil. Electronic address: rapelaac@yahoo.com.br.
authors.forename: Angela C R
authors.initials: AC
authors.lastname: Medeiros
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: britomef@cpqam.fiocruz.br.
authors.forename: Maria E F
authors.initials: ME
authors.lastname: Brito
authors.affiliation: Institut National de la Santé et la Recherche Médicale (INSERM-U906), France. Electronic address: alain.dessein@univ-amu.fr.
authors.forename: Alain J J
authors.initials: AJ
authors.lastname: Dessein
authors.affiliation: Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: valeriaph@gmail.com.
authors.forename: Valéria R A
authors.initials: VR
authors.lastname: Pereira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000953:Antigens, Protozoan / Q000494:pharmacology; D016022:Case-Control Studies; D045424:Complex Mixtures / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D007892:Leishmania braziliensis / Q000737:chemistry / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D045424:Complex Mixtures; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539900:RORC protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: American tegumentary leishmaniasis; Antigens; Cytokines; Gene expression; Immune response