title: Protective Profile Involving CD23/IgE-mediated NO Release is a Hallmark of Cutaneous Leishmaniasis Patients from the Xakriabá Indigenous Community in Minas Gerais, Brazil.
abstract: In this study, we described, for the first time, specific aspects of an anti-Leishmania immune response in a Brazilian Xakriabá indigenous community. Induction of an intracellular NO pathway, triggered by the binding of IgE to CD23 receptor in IFN-γ/IL-4 cytokines environment, was evaluated in localized cutaneous leishmaniasis (LCL) carriers and positive Montenegro skin test (MST) individuals without skin lesion (MT(+) SL(-)). Our data demonstrated that the higher frequency of CD23(+) CD14(+) monocytes and the increased serum levels of IgE observed in the LCL group were even higher in LCL carriers with late lesions (LCL≥60). Furthermore, patients with LCL presented increased NO production after Leishmania (Viannia) braziliensis stimulation and this NO profile was independent of the time of the lesion (recent LCL<60 or late LCL≥60). We also showed that the increased frequency of IFN-γ(+) and IL-4(+) CD4(+) T cells is related to the MT(+) SL(-) group. The results of biomarker signature curves demonstrated that in the MT(+) SL(-) group, the index signature was characterized by DAF-2T(+) CD14(+)/IL-4(+) CD8(+)/IFN-γ(+) CD4(+)/IL-4(+) CD4(+). On the other hand, the LCL group presented a higher index of DAF-2T(+) CD14(+)/CD23(+) CD14(+)/IL-4(+) CD8(+), associated with a lower index of IFN-γ(+) CD8(+). Considering the time of lesion, data analysis demonstrated that the main differences observed were highlighted in LCL<60 patients, with a higher index of CD23(+) CD14(+), which was also present in LCL≥60 patients. In conclusion, our data suggest that the protective immune response involving CD23-IgE-mediated NO release is a hallmark of patients with LCL. However, in MT(+) SL(-) individuals, another different leishmanicidal mechanism seems to be involved.
authors: Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors: R
authors: R
authors: Carvalho-Gontijo
authors: Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors: V
authors: V
authors: Peruhype-Magalhães
authors: Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors: M F
authors: MF
authors: Costa-Silva
authors: Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors: O A
authors: OA
authors: Martins-Filho
authors: Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors: P F
authors: PF
authors: Quaresma
authors: Laboratory of Leishmaniasis, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors: J de Moura
authors: Jde M
authors: Freire
authors: Center of Hematology and Hemotherapy Foundation of Minas Gerais - Hemominas, Belo Horizonte, MG, Brazil.
authors: E de Castro
authors: Ede C
authors: Moreno
authors: Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors: A
authors: A
authors: Teixeira-Carvalho
authors: Laboratory of Leishmaniasis, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors: C M Ferreira
authors: CM
authors: Gontijo
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000097:blood / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000276:immunology* / Q000378:metabolism; D044382:Population Groups; D017455:Receptors, IgE / Q000097:blood / Q000276:immunology*; D012882:Skin Tests / Q000379:methods; D055815:Young Adult
chemical_list: D018950:Lipopolysaccharide Receptors; D017455:Receptors, IgE; D015847:Interleukin-4; D009569:Nitric Oxide; D007073:Immunoglobulin E; D007371:Interferon-gamma