Regulatory T Cells and Pro-inflammatory Responses Predominate in Children with Tuberculosis
BackgroundFollowing infection with Mycobacterium tuberculosis (M.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. The exact mechanisms required for containment of M.tb are not known, but would be important to identify correlates of protection.Obj...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00448/full |
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| author | Elizabeth Whittaker Elizabeth Whittaker Mark Nicol Heather J. Zar Heather J. Zar Beate Kampmann Beate Kampmann |
| author_facet | Elizabeth Whittaker Elizabeth Whittaker Mark Nicol Heather J. Zar Heather J. Zar Beate Kampmann Beate Kampmann |
| author_sort | Elizabeth Whittaker |
| collection | DOAJ |
| description | BackgroundFollowing infection with Mycobacterium tuberculosis (M.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. The exact mechanisms required for containment of M.tb are not known, but would be important to identify correlates of protection.ObjectiveTo comprehensively analyze key immune responses to mycobacteria between HIV-negative children with extrapulmonary TB (EPTB) compared to children with pulmonary TB (PTB) or healthy controls.MethodsWhole blood was stimulated in vitro with mycobacteria for 24 h or 6 days to induce effector and memory responses. CD4, CD8, γδ, regulatory T cells, and their related cytokines were measured. Samples of children with tuberculosis (TB) disease were analyzed both at time of diagnosis and at the end of TB treatment to determine if any differences were due to TB disease or an underlying host phenotype.ResultsSeventy-six children with TB disease (48 with PTB and 28 with EPTB) and 83 healthy controls were recruited to the study. The frequency of CD4+CD25+CD39+FOXP3+ regulatory T cells and secreted IL10 were significantly higher in children with TB compared to healthy controls. IFNγ-, IL17-, and IL22-producing γδ T cells, IL22-producing CD4+ T cells and secreted pro-inflammatory cytokines (IFNγ, IL1β, and TNFα) were significantly lower in children with TB disease compared to healthy controls. IFNγ-producing CD4+ T cells and Ki67+-proliferating CD4+ T cells, however, were present in equal numbers in both groups. Following treatment, these immune parameters recovered to “healthy” levels or greater in children with PTB, but not those with extrapulmonary TB.ConclusionIn children with TB disease, a predominantly immune regulatory state is present. These immune findings do not distinguish between children with PTB and EPTB at the time of diagnosis. Following treatment, these inflammatory responses recover in PTB, suggesting that the effect is disease specific rather than due to an underlying host defect. |
| first_indexed | 2024-12-20T06:49:11Z |
| format | Article |
| id | doaj.art-257ba1b44e0a4b10b1d57250b692039e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T06:49:11Z |
| publishDate | 2017-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-257ba1b44e0a4b10b1d57250b692039e2022-12-21T19:49:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-04-01810.3389/fimmu.2017.00448258352Regulatory T Cells and Pro-inflammatory Responses Predominate in Children with TuberculosisElizabeth Whittaker0Elizabeth Whittaker1Mark Nicol2Heather J. Zar3Heather J. Zar4Beate Kampmann5Beate Kampmann6Academic Department of Paediatrics, Imperial College London, London, UKUCT Faculty of Health Sciences, Division of Medical Microbiology, Department of Clinical Laboratory Sciences, Institute of Infectious Disease and Molecular Medicine, Cape Town, South AfricaUCT Faculty of Health Sciences, Division of Medical Microbiology, Department of Clinical Laboratory Sciences, Institute of Infectious Disease and Molecular Medicine, Cape Town, South AfricaMRC Unit of Child and Adolescent Health, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, Cape Town, South AfricaAcademic Department of Paediatrics, Imperial College London, London, UKVaccines and Immunity Theme, MRC Unit The Gambia, Fajara, GambiaBackgroundFollowing infection with Mycobacterium tuberculosis (M.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. The exact mechanisms required for containment of M.tb are not known, but would be important to identify correlates of protection.ObjectiveTo comprehensively analyze key immune responses to mycobacteria between HIV-negative children with extrapulmonary TB (EPTB) compared to children with pulmonary TB (PTB) or healthy controls.MethodsWhole blood was stimulated in vitro with mycobacteria for 24 h or 6 days to induce effector and memory responses. CD4, CD8, γδ, regulatory T cells, and their related cytokines were measured. Samples of children with tuberculosis (TB) disease were analyzed both at time of diagnosis and at the end of TB treatment to determine if any differences were due to TB disease or an underlying host phenotype.ResultsSeventy-six children with TB disease (48 with PTB and 28 with EPTB) and 83 healthy controls were recruited to the study. The frequency of CD4+CD25+CD39+FOXP3+ regulatory T cells and secreted IL10 were significantly higher in children with TB compared to healthy controls. IFNγ-, IL17-, and IL22-producing γδ T cells, IL22-producing CD4+ T cells and secreted pro-inflammatory cytokines (IFNγ, IL1β, and TNFα) were significantly lower in children with TB disease compared to healthy controls. IFNγ-producing CD4+ T cells and Ki67+-proliferating CD4+ T cells, however, were present in equal numbers in both groups. Following treatment, these immune parameters recovered to “healthy” levels or greater in children with PTB, but not those with extrapulmonary TB.ConclusionIn children with TB disease, a predominantly immune regulatory state is present. These immune findings do not distinguish between children with PTB and EPTB at the time of diagnosis. Following treatment, these inflammatory responses recover in PTB, suggesting that the effect is disease specific rather than due to an underlying host defect.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00448/fulltuberculosisextrapulmonarypediatricmycobacterial immunityregulatory T cells |
| spellingShingle | Elizabeth Whittaker Elizabeth Whittaker Mark Nicol Heather J. Zar Heather J. Zar Beate Kampmann Beate Kampmann Regulatory T Cells and Pro-inflammatory Responses Predominate in Children with Tuberculosis Frontiers in Immunology tuberculosis extrapulmonary pediatric mycobacterial immunity regulatory T cells |
| title | Regulatory T Cells and Pro-inflammatory Responses Predominate in Children with Tuberculosis |
| title_full | Regulatory T Cells and Pro-inflammatory Responses Predominate in Children with Tuberculosis |
| title_fullStr | Regulatory T Cells and Pro-inflammatory Responses Predominate in Children with Tuberculosis |
| title_full_unstemmed | Regulatory T Cells and Pro-inflammatory Responses Predominate in Children with Tuberculosis |
| title_short | Regulatory T Cells and Pro-inflammatory Responses Predominate in Children with Tuberculosis |
| title_sort | regulatory t cells and pro inflammatory responses predominate in children with tuberculosis |
| topic | tuberculosis extrapulmonary pediatric mycobacterial immunity regulatory T cells |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00448/full |
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