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INTERPLAY AMONG DIFFERENTIAL EXPOSURE TO MYCOBACTERIUM LEPRAE AND TLR4 POLYMORPHISM IMPACTS THE IMMUNE RESPONSE IN HOUSEHOLD CONTACTS OF LEPROSY PATIENTS
Quimiocinas e citocinas
Fatores imunológicos
Fatores genéticos
gene TLR4
Chemokines and cytokines
Immunological factors
Genetic factors
TLR4 gene
Autor
Cunha, Eloisa Helena Medeiros
Marçal, Pedro Henrique Ferreira
Gama, Rafael Silva
Oliveira, Lorena Bruna Pereira de
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Sousa, Joaquim Pedro Brito de
Souza, Márcio Luís Moreira de
Fairley, Jessica Kathleen
Valente, Thaisa Netto Souza
Rodrigues, Cibele Velloso
Martins Filho, Olindo Assis
Oliveira, Dirce Ribeiro de
Fraga, Lucia Alves de Oliveira
Marçal, Pedro Henrique Ferreira
Gama, Rafael Silva
Oliveira, Lorena Bruna Pereira de
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Sousa, Joaquim Pedro Brito de
Souza, Márcio Luís Moreira de
Fairley, Jessica Kathleen
Valente, Thaisa Netto Souza
Rodrigues, Cibele Velloso
Martins Filho, Olindo Assis
Oliveira, Dirce Ribeiro de
Fraga, Lucia Alves de Oliveira
Afiliación
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil / Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil / Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil /Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United States.
Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.
Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz, Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brasil..
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United States.
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Fundação Oswaldo Cruz, Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brasil..
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil / Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil /Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United States.
Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.
Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz, Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brasil..
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United States.
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Fundação Oswaldo Cruz, Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brasil..
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.
Resumen en ingles
Introduction: The aim of the present study was to investigate the association
between the single nucleotide polymorphism (SNP) rs1927914 A/G in TLR4 gene
and the immunological profile of household contacts (HHC) of leprosy patients.
Leprosy classification is usually complex and requires the assessment of several
clinical and laboratorial features.
Methods: Herein, we have applied distinct models of descriptive analysis to
explore qualitative/quantitative changes in chemokine and cytokine production
in HHC further categorized according to operational classification [HHC(PB) and
HHC(MB)] and according to TLR4SNP.
Results and discussion: Our results showed that M. leprae stimuli induced an
outstanding production of chemokines (CXCL8;CCL2; CXCL9; CXCL10) by HHC
(PB), while increase levels of pro-inflammatory cytokines (IL-6; TNF; IFN-g; IL-17)
were observed for HHC(MB). Moreover, the analysis of chemokine and cytokine
signatures demonstrated that A allele was associated with a prominent soluble
mediator secretion (CXCL8; CXCL9; IL-6; TNF; IFN-g). Data analysis according to
TLR4 SNP genotypes further demonstrated that AA and AG were associated with
a more prominent secretion of soluble mediators as compared to GG, supporting
the clustering of AA and AG genotypes into dominant genetic model. CXCL8, IL-
6, TNF and IL-17 displayed distinct profiles in HHC(PB) vs HHC(MB) or AA+AG vs
GG genotype. In general, chemokine/cytokine networks analysis showed overall profile of AA+GA-selective (CXCL9–CXCL10) and GG-selective
(CXCL10–IL-6) axis regardless of the operational classification. However,
mirrored inverted CCL2–IL-10 axis and a (IFN-g–IL-2)-selective axis were
identified in HHC(MB). CXCL8 presented outstanding performance to classify
AA+AG from GG genotypes and HHC(PB) from HHC(MB). TNF and IL-17
presented elevated accuracy to classify AA+AG from GG genotypes and HHC
(PB) (low levels) from HHC(MB) (high levels), respectively. Our results highlighted
that both factors: i) differential exposure to M. leprae and ii) TLR4 rs1927914
genetic background impact the immune response of HHC. Our main results
reinforce the relevance of integrated studies of immunological and genetic
biomarkers that may have implications to improve the classification and
monitoring of HHC in future studies.
Palabras clave en portugues
HanseníaseQuimiocinas e citocinas
Fatores imunológicos
Fatores genéticos
gene TLR4
Palabras clave en ingles
LeprosyChemokines and cytokines
Immunological factors
Genetic factors
TLR4 gene
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