Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
IntroductionThe 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...
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1130137/full |
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| author | Eloisa Helena Medeiros Cunha Eloisa Helena Medeiros Cunha Pedro Henrique Ferreira Marçal Pedro Henrique Ferreira Marçal Pedro Henrique Ferreira Marçal Rafael Silva Gama Lorena Bruna Pereira de Oliveira Roberta Olmo Pinheiro Euzenir Nunes Sarno Joaquim Pedro Brito-de-Sousa Márcio Luís Moreira de Souza Jessica Kathleen Fairley Thaisa Netto Souza Valente Cibele Velloso-Rodrigues Olindo Assis Martins-Filho Dirce Ribeiro de Oliveira Lucia Alves de Oliveira Fraga |
| author_facet | Eloisa Helena Medeiros Cunha Eloisa Helena Medeiros Cunha Pedro Henrique Ferreira Marçal Pedro Henrique Ferreira Marçal Pedro Henrique Ferreira Marçal Rafael Silva Gama Lorena Bruna Pereira de Oliveira Roberta Olmo Pinheiro Euzenir Nunes Sarno Joaquim Pedro Brito-de-Sousa Márcio Luís Moreira de Souza Jessica Kathleen Fairley Thaisa Netto Souza Valente Cibele Velloso-Rodrigues Olindo Assis Martins-Filho Dirce Ribeiro de Oliveira Lucia Alves de Oliveira Fraga |
| author_sort | Eloisa Helena Medeiros Cunha |
| collection | DOAJ |
| description | IntroductionThe 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.MethodsHerein, 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 discussionOur 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-γ; 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-γ). 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 an 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-γ–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. |
| first_indexed | 2024-04-09T15:33:39Z |
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| id | doaj.art-bd372c38fa88494ab209f968a1e168f3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T15:33:39Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bd372c38fa88494ab209f968a1e168f32023-04-28T05:28:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11301371130137Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patientsEloisa Helena Medeiros Cunha0Eloisa Helena Medeiros Cunha1Pedro Henrique Ferreira Marçal2Pedro Henrique Ferreira Marçal3Pedro Henrique Ferreira Marçal4Rafael Silva Gama5Lorena Bruna Pereira de Oliveira6Roberta Olmo Pinheiro7Euzenir Nunes Sarno8Joaquim Pedro Brito-de-Sousa9Márcio Luís Moreira de Souza10Jessica Kathleen Fairley11Thaisa Netto Souza Valente12Cibele Velloso-Rodrigues13Olindo Assis Martins-Filho14Dirce Ribeiro de Oliveira15Lucia Alves de Oliveira Fraga16Universidade Federal de Juiz de Fora, Governador Valadares, MG, BrazilUniversidade Vale do Rio Doce – Univale, Department of Health Sciences, Governador Valadares, MG, BrazilUniversidade Federal de Juiz de Fora, Governador Valadares, MG, BrazilUniversidade Vale do Rio Doce – Univale, Department of Health Sciences, Governador Valadares, MG, BrazilDivision of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United StatesUniversidade Vale do Rio Doce – Univale, Department of Health Sciences, Governador Valadares, MG, BrazilUniversidade Vale do Rio Doce – Univale, Department of Health Sciences, Governador Valadares, MG, BrazilLaboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz –FIOCRUZ-RJ, Rio de Janeiro, RJ, BrazilLaboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz –FIOCRUZ-RJ, Rio de Janeiro, RJ, BrazilGrupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, FIOCRUZ-Minas, Belo Horizonte, MG, BrazilUniversidade Federal de Juiz de Fora, Governador Valadares, MG, BrazilDivision of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United StatesUniversidade Federal de Juiz de Fora, Governador Valadares, MG, BrazilUniversidade Federal de Juiz de Fora, Governador Valadares, MG, BrazilGrupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, FIOCRUZ-Minas, Belo Horizonte, MG, BrazilUniversidade Federal de Juiz de Fora, Governador Valadares, MG, BrazilUniversidade Federal de Juiz de Fora, Governador Valadares, MG, BrazilIntroductionThe 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.MethodsHerein, 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 discussionOur 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-γ; 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-γ). 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 an 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-γ–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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1130137/fullleprosychemokines and cytokinesimmunological factorsgenetic factorsTLR4 gene |
| spellingShingle | Eloisa Helena Medeiros Cunha Eloisa Helena Medeiros Cunha Pedro Henrique Ferreira Marçal Pedro Henrique Ferreira Marçal Pedro Henrique Ferreira Marçal Rafael Silva Gama Lorena Bruna Pereira de Oliveira Roberta Olmo Pinheiro Euzenir Nunes Sarno Joaquim Pedro Brito-de-Sousa Márcio Luís Moreira de Souza Jessica Kathleen Fairley Thaisa Netto Souza Valente Cibele Velloso-Rodrigues Olindo Assis Martins-Filho Dirce Ribeiro de Oliveira Lucia Alves de Oliveira Fraga Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients Frontiers in Immunology leprosy chemokines and cytokines immunological factors genetic factors TLR4 gene |
| title | Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients |
| title_full | Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients |
| title_fullStr | Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients |
| title_full_unstemmed | Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients |
| title_short | Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients |
| title_sort | interplay among differential exposure to mycobacterium leprae and tlr4 polymorphism impacts the immune response in household contacts of leprosy patients |
| topic | leprosy chemokines and cytokines immunological factors genetic factors TLR4 gene |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1130137/full |
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