Document Detail


CXCR5⁺ T helper cells mediate protective immunity against tuberculosis.
MedLine Citation:
PMID:  23281399     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One third of the world's population is infected with Mycobacterium tuberculosis (Mtb). Although most infected people remain asymptomatic, they have a 10% lifetime risk of developing active tuberculosis (TB). Thus, the current challenge is to identify immune parameters that distinguish individuals with latent TB from those with active TB. Using human and experimental models of Mtb infection, we demonstrated that organized ectopic lymphoid structures containing CXCR5+ T cells were present in Mtb-infected lungs. In addition, we found that in experimental Mtb infection models, the presence of CXCR5+ T cells within ectopic lymphoid structures was associated with immune control. Furthermore, in a mouse model of Mtb infection, we showed that activated CD4+CXCR5+ T cells accumulated in Mtb-infected lungs and produced proinflammatory cytokines. Mice deficient in Cxcr5 had increased susceptibility to TB due to defective T cell localization within the lung parenchyma. We demonstrated that CXCR5 expression in T cells mediated correct T cell localization within TB granulomas, promoted efficient macrophage activation, protected against Mtb infection, and facilitated lymphoid follicle formation. These data demonstrate that CD4+CXCR5+ T cells play a protective role in the immune response against TB and highlight their potential use for future TB vaccine design and therapy.
Authors:
Samantha R Slight; Javier Rangel-Moreno; Radha Gopal; Yinyao Lin; Beth A Fallert Junecko; Smriti Mehra; Moises Selman; Enrique Becerril-Villanueva; Javier Baquera-Heredia; Lenin Pavon; Deepak Kaushal; Todd A Reinhart; Troy D Randall; Shabaana A Khader
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2013-09-13    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  712-26     Citation Subset:  AIM; IM    
Affiliation:
Department of Pediatrics, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytokines / biosynthesis
Disease Models, Animal
Female
Granuloma, Respiratory Tract / immunology
Humans
Inflammation Mediators / metabolism
Latent Tuberculosis / immunology*
Lung / immunology,  microbiology
Lymphocyte Activation
Lymphoid Tissue / immunology
Macrophage Activation
Male
Mice
Mice, Knockout
Mice, Transgenic
Receptors, CXCR5 / metabolism*
T-Lymphocyte Subsets / immunology
T-Lymphocytes, Helper-Inducer / immunology*
Tuberculosis, Pulmonary / immunology*
Grant Support
ID/Acronym/Agency:
AI060422/AI/NIAID NIH HHS; AI083541/AI/NIAID NIH HHS; AI091457/AI/NIAID NIH HHS; AI91036/AI/NIAID NIH HHS; HL105427/HL/NHLBI NIH HHS; HL69409/HL/NHLBI NIH HHS; R01 HL069409/HL/NHLBI NIH HHS; R01 HL105427/HL/NHLBI NIH HHS; RR000164/RR/NCRR NIH HHS; RR020159/RR/NCRR NIH HHS; RR026006/RR/NCRR NIH HHS; T32 AI065380-08/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Blr1 protein, mouse; 0/Cytokines; 0/Inflammation Mediators; 0/Receptors, CXCR5
Comments/Corrections

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