Document Detail


Abnormal immune responses in persons with previous extrapulmonary tuberculosis in an in vitro model that simulates in vivo infection with Mycobacterium tuberculosis.
MedLine Citation:
PMID:  22675156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Persons with previous extrapulmonary tuberculosis have reduced peripheral blood mononuclear cell cytokine production and CD4(+) lymphocytes compared to persons with previous pulmonary tuberculosis or latent tuberculosis infection, but specific defects related to Mycobacterium tuberculosis infection of macrophages have not been characterized. The objective of this study was to further characterize the in vitro immune responses to M. tuberculosis infection in HIV-seronegative persons with previous extrapulmonary tuberculosis. Peripheral blood mononuclear cells were isolated from HIV-seronegative persons with previous extrapulmonary tuberculosis (n = 11), previous pulmonary tuberculosis (n = 21), latent M. tuberculosis infection (n = 19), and uninfected tuberculosis contacts (n = 20). Experimental conditions included M. tuberculosis-infected macrophages cultured with and without monocyte-depleted peripheral blood mononuclear cells. Concentrations of interleukin 1β (IL-1β), IL-4, IL-6, CXCL8 (IL-8), IL-10, IL-12p70, IL-17, CCL2 (monocyte chemoattractant protein 1), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) were measured by multiplex cytokine array. When M. tuberculosis-infected macrophages were cocultured with monocyte-depleted peripheral blood mononuclear cells, IFN-γ (P = 0.01), TNF-α (P = 0.04), IL-10 (P < 0.001), and IL-6 (P = 0.03) exhibited similar continua of responses, with uninfected persons producing the lowest levels, followed by extrapulmonary tuberculosis cases, pulmonary tuberculosis controls, and persons with latent M. tuberculosis infection. A similar pattern was observed with CXCL8 (P = 0.04), IL-10 (P = 0.02), and CCL2 (P = 0.03) when monocyte-depleted peripheral blood mononuclear cells from the four groups were cultured alone. Persons with previous extrapulmonary tuberculosis had decreased production of several cytokines, both at rest and after stimulation with M. tuberculosis. Our results suggest that persons who develop extrapulmonary tuberculosis have a subtle global immune defect that affects their response to M. tuberculosis infection.
Authors:
Christina T Fiske; Alexandre S de Almeida; Ayumi K Shintani; Spyros A Kalams; Timothy R Sterling
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-06
Journal Detail:
Title:  Clinical and vaccine immunology : CVI     Volume:  19     ISSN:  1556-679X     ISO Abbreviation:  Clin. Vaccine Immunol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-02     Completed Date:  2012-12-06     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101252125     Medline TA:  Clin Vaccine Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1142-9     Citation Subset:  IM    
Affiliation:
Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. christina.fiske@vanderbilt.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Cells, Cultured
Coculture Techniques / methods
Cytokines / secretion
Female
Humans
Leukocytes, Mononuclear / immunology
Macrophages / immunology,  microbiology
Male
Middle Aged
Mycobacterium tuberculosis / immunology*
Tuberculosis / immunology*
Grant Support
ID/Acronym/Agency:
K23 AI091692/AI/NIAID NIH HHS; K24 AI065298/AI/NIAID NIH HHS; K24 AI065298/AI/NIAID NIH HHS; KL2 RR024977/RR/NCRR NIH HHS; KL2 TR000446/TR/NCATS NIH HHS; P30 AI 54999/AI/NIAID NIH HHS; P60 AR056116/AR/NIAMS NIH HHS; TL1 RR024978/RR/NCRR NIH HHS; TL1 TR000447/TR/NCATS NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 TR000445/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines
Comments/Corrections

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