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Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFα production induced by Gram-positive and Gram-negative bacteria

Genes & Immunity volume 4, pages 283–288 (2003)Cite this article

Abstract

Improved understanding of how host genetic variation affects resistance to microbial pathogens could lead to better treatment and/or prevention of infectious diseases. The lymphotoxin alpha (LTA)+250 and CD14−159 polymorphisms are associated with differences in susceptibility or outcome to several infections. We stimulated peripheral blood mononuclear cells (PBMC) from 22 healthy individuals with purified lipopolysaccharide (LPS), heat-killed Escherichia coli or Streptococcus pneumoniae. TNFαintracellular protein levels were measured by flow cytometry and mRNA was quantitated by RT-PCR. TNFα mRNA levels were higher in LTA+250GG subjects after 4 h incubation with LPS compared with LTA+250AA (T test, P=0.001). In contrast, after 8 h incubation with S. pneumoniae, there was slightly more TNFα mRNA in cells from LTA+250AA subjects. After 4 h incubation with LPS or E. coli, CD14−159TT subjects had higher TNFα mRNA levels than CD14−159CC (P=0.05, 0.033, respectively). Neither polymorphism affected the proportion of cells expressing intracellular TNFα protein. This suggests that the polymorphisms affected transcription and that other regulatory mechanisms affect production of TNFα protein. The effect of these two polymorphisms on TNFα mRNA production is stimulus dependent, with opposite effects observed for Gram-positive and Gram-negative stimuli.

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Acknowledgements

We thank John Boehm from the Department of Microbiology, Royal Perth Hospital, for advice and assistance with the culturing of the bacteria, and Rom Krueger from the Department of Haematology, Royal Perth Hospital, for expert assistance with flow cytometry.

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Authors and Affiliations

  1. Department of Medicine, University of Western Australia, Western Australia

    S E L Temple, K Y Cheong, C M Almeida & G W Waterer

  2. Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital,

    P Price

  3. Department of Pathology, University of Western Australia, Western Australia

    P Price

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  1. S E L Temple
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Correspondence to S E L Temple.

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This work was funded by Genomics Collaborative Inc. (America) and the Raine Medical Research Foundation of Western Australia.

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Temple, S., Cheong, K., Almeida, C. et al. Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFα production induced by Gram-positive and Gram-negative bacteria. Genes Immun 4, 283–288 (2003). https://doi.org/10.1038/sj.gene.6363963

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