Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 401K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flores-Villanueva, P. O. Articles by Granados, J. Search for Related Content PubMed PubMed Citation Articles by Flores-Villanueva, P. O. Articles by Granados, J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM Protein UniGene Substance via MeSH Related Collections Related Article Social Bookmarking                      What's this?

¹ Center for Biomedical Research, University of Texas Health Center at Tyler, Tyler, TX 75708
² Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea
³ Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02115
⁴ Mexican Institute of Respiratory Diseases, Mexico D.F. 14080, Mexico
⁵ Department of Immunology and Rheumatology, Mexican National Institute of Medicine and Nutrition "Salvador Zubiran," Mexico D.F. 14000, Mexico

CORRESPONDENCE Pedro O. Flores-Villanueva: pedro.flores{at}UTHCT.edu

We examined the distribution of single nucleotide polymorphisms (SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein–1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein–1 genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti–MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis–stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis–stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis.

Abbreviations used: ANOVA, analysis of variance; BCG, Bacillus Calmette-Guerin; BMI, body mass index; CI, confidence interval; MCP-1, monocyte chemoattractant protein–1; MIP-1, macrophage inflammatory protein–1; NOS2A, nitric oxide synthase 2A; OR, odds ratio; RANTES, regulated on activation, normal T cell expressed and secreted; SNP, single nucleotide polymorphism.

P.O. Flores-Villanueva and J.A. Ruiz-Morales contributed equally to this work.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Chemokine drives tuberculosis

Heather L. Van Epps
J. Exp. Med. 2005 202: 1614. [Full Text] [PDF]

This article has been cited by other articles:

• Thye, T., Nejentsev, S., Intemann, C. D., Browne, E. N., Chinbuah, M. A., Gyapong, J., Osei, I., Owusu-Dabo, E., Zeitels, L. R., Herb, F., Horstmann, R. D., Meyer, C. G. (2009). MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa. Hum Mol Genet 18: 381-388 [Abstract] [Full Text]  
• Mendez-Samperio, P., Trejo, A., Perez, A. (2008). Mycobacterium bovis Bacillus Calmette-Guerin Induces CCL5 Secretion via the Toll-Like Receptor 2-NF-{kappa}B and -Jun N-Terminal Kinase Signaling Pathways. CVI 15: 277-283 [Abstract] [Full Text]  
• Sterling, T. R., Martire, T., de Almeida, A. S., Ding, L., Greenberg, D. E., Moreira, L. A., Elloumi, H., Torres, A. P.V., Sant'Anna, C. C., Calazans, E., Paraguassu, G., Gebretsadik, T., Shintani, A., Miller, K., Kritski, A., e Silva, J. R. L., Holland, S. M. (2007). Immune Function in Young Children With Previous Pulmonary or Miliary/Meningeal Tuberculosis and Impact of BCG Vaccination. Pediatrics 120: e912-e921 [Abstract] [Full Text]  
• van de Sande, W. W. J., Fahal, A., Verbrugh, H., van Belkum, A. (2007). Polymorphisms in Genes Involved in Innate Immunity Predispose Toward Mycetoma Susceptibility. J. Immunol. 179: 3065-3074 [Abstract] [Full Text]  
• Chakravarty, S. D., Xu, J., Lu, B., Gerard, C., Flynn, J., Chan, J. (2007). The Chemokine Receptor CXCR3 Attenuates the Control of Chronic Mycobacterium tuberculosis Infection in BALB/c Mice. J. Immunol. 178: 1723-1735 [Abstract] [Full Text]  
• Baghdadi, J. E., Orlova, M., Alter, A., Ranque, B., Chentoufi, M., Lazrak, F., Archane, M. I., Casanova, J.-L., Benslimane, A., Schurr, E., Abel, L. (2006). An autosomal dominant major gene confers predisposition to pulmonary tuberculosis in adults. JEM 203: 1679-1684 [Abstract] [Full Text]  
• Alcais, A., Fieschi, C., Abel, L., Casanova, J.-L. (2005). Tuberculosis in children and adults: two distinct genetic diseases. JEM 202: 1617-1621 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS