American tegumentary leishmaniasis: mRNA expression for Th1 and Treg mediators are predominant in patients with recent active disease

Marina A Souza; Thays M Almeida; Maria Carolina A B Castro; Andresa P Oliveira-Mendes; Amanda F Almeida; Beatriz C Oliveira; Lucas F Rocha; Angela C R Medeiros; Maria E F Brito; Alain J J Dessein; Valéria R A Pereira

doi:10.1016/j.imbio.2015.08.009

American tegumentary leishmaniasis: mRNA expression for Th1 and Treg mediators are predominant in patients with recent active disease

Immunobiology. 2016 Feb;221(2):253-9. doi: 10.1016/j.imbio.2015.08.009. Epub 2015 Aug 14.

Affiliations

¹ Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].
² Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].
³ Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].
⁴ Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].
⁵ Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].
⁶ Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].
⁷ Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].
⁸ Hospital Universitário Oswaldo Cruz, Universidade de Pernambuco (HUOC/UPE), Brazil. Electronic address: [email protected].
⁹ Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].
¹⁰ Institut National de la Santé et la Recherche Médicale (INSERM-U906), France. Electronic address: [email protected].
¹¹ Laboratory of Immunogenetics, Immunology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation (CPqAM/FIOCRUZ), Brazil. Electronic address: [email protected].

PMID: 26572279
DOI: 10.1016/j.imbio.2015.08.009

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.

Keywords: American tegumentary leishmaniasis; Antigens; Cytokines; Gene expression; Immune response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Antigens, Protozoan / pharmacology
Case-Control Studies
Complex Mixtures / pharmacology
Female
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / immunology
Gene Expression Regulation / drug effects
Humans
Interferon-gamma / genetics
Interferon-gamma / immunology
Interleukins / genetics
Interleukins / immunology
Leishmania braziliensis / chemistry
Leishmania braziliensis / immunology*
Leishmaniasis, Cutaneous / genetics
Leishmaniasis, Cutaneous / immunology*
Leishmaniasis, Cutaneous / parasitology
Leishmaniasis, Cutaneous / pathology
Male
Middle Aged
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
Primary Cell Culture
RNA, Messenger / genetics
RNA, Messenger / immunology*
T-Lymphocytes, Regulatory / drug effects
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / parasitology
Th1 Cells / drug effects
Th1 Cells / immunology*
Th1 Cells / parasitology
Transforming Growth Factor beta / genetics
Transforming Growth Factor beta / immunology
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / immunology

Substances

Antigens, Protozoan
Complex Mixtures
FOXP3 protein, human
Forkhead Transcription Factors
Interleukins
Nuclear Receptor Subfamily 1, Group F, Member 3
RNA, Messenger
RORC protein, human
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha
Interferon-gamma