Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Temperature triggers immune evasion by Neisseria meningitidis

Nature volume 502, pages 237–240 (2013)Cite this article

Subjects

Abstract

Neisseria meningitidis has several strategies to evade complement-mediated killing, and these contribute to its ability to cause septicaemic disease and meningitis. However, the meningococcus is primarily an obligate commensal of the human nasopharynx, and it is unclear why the bacterium has evolved exquisite mechanisms to avoid host immunity. Here we demonstrate that mechanisms of meningococcal immune evasion and resistance against complement increase in response to an increase in ambient temperature. We have identified three independent RNA thermosensors located in the 5′ untranslated regions of genes necessary for capsule biosynthesis, the expression of factor H binding protein, and sialylation of lipopolysaccharide, which are essential for meningococcal resistance against immune killing1,2. Therefore increased temperature (which occurs during inflammation) acts as a ‘danger signal’ for the meningococcus, enhancing its defence against human immune killing. Infection with viral pathogens, such as influenza, leads to inflammation in the nasopharynx with an increased temperature and recruitment of immune effectors3,4. Thermoregulation of immune defence could offer an adaptive advantage to the meningococcus during co-infection with other pathogens, and promote the emergence of virulence in an otherwise commensal bacterium.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Loss of 8 bp increases capsule expression and complement resistance.
Figure 2: Capsule gene expression is governed by an RNA thermosensor.
Figure 3: Thermosensing of immune evasion mechanisms.
Figure 4: Temperature influences complement escape by N. meningitidis.

Similar content being viewed by others

References

  1. Schneider, M. C. et al. Functional significance of factor H binding to Neisseria meningitidis. J. Immunol. 176, 7566–7575 (2006)

    Article  CAS  Google Scholar 

  2. Schneider, M. C. et al. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature 458, 890–893 (2009)

    Article  ADS  CAS  Google Scholar 

  3. Bjornson, A. B., Mellencamp, M. A. & Schiff, G. M. Complement is activated in the upper respiratory tract during influenza virus infection. Am. Rev. Respir. Dis. 143, 1062–1066 (1991)

    Article  CAS  Google Scholar 

  4. Gentile, D. et al. Increased interleukin-6 levels in nasal lavage samples following experimental influenza A virus infection. Clin. Diagn. Lab. Immunol. 5, 604–608 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Stephens, D. S., Greenwood, B. & Brandtzaeg, P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 369, 2196–2210 (2007)

    Article  Google Scholar 

  6. Cartwright, K. A. et al. Influenza A and meningococcal disease. Lancet 338, 554–557 (1991)

    Article  CAS  Google Scholar 

  7. Schneider, M. C., Exley, R. M., Ram, S., Sim, R. B. & Tang, C. M. Interactions between Neisseria meningitidis and the complement system. Trends Microbiol. 15, 233–240 (2007)

    Article  CAS  Google Scholar 

  8. Stephens, D. S., Spellman, P. A. & Swartley, J. S. Effect of the (α2→8)-linked polysialic acid capsule on adherence of Neisseria meningitidis to human mucosal cells. J. Infect. Dis. 167, 475–478 (1993)

    Article  CAS  Google Scholar 

  9. Hammerschmidt, S. et al. Contribution of genes from the capsule gene complex (cps) to lipooligosaccharide biosynthesis and serum resistance in Neisseria meningitidis. Mol. Microbiol. 11, 885–896 (1994)

    Article  CAS  Google Scholar 

  10. Tzeng, Y. L. et al. Transcriptional regulation of divergent capsule biosynthesis and transport operon promoters in serogroup B Neisseria meningitidis. Infect. Immun. 69, 2502–2511 (2001)

    Article  CAS  Google Scholar 

  11. Uria, M. J. et al. A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies. J. Exp. Med. 205, 1423–1434 (2008)

    Article  CAS  Google Scholar 

  12. Ganguli, S. et al. Molecular cloning and analysis of genes for sialic acid synthesis in Neisseria meningitidis group B and purification of the meningococcal CMP-NeuNAc synthetase enzyme. J. Bacteriol. 176, 4583–4589 (1994)

    Article  CAS  Google Scholar 

  13. van der Ende, A., Hopman, C. T. & Dankert, J. Multiple mechanisms of phase variation of PorA in Neisseria meningitidis. Infect. Immun. 68, 6685–6690 (2000)

    Article  CAS  Google Scholar 

  14. von Loewenich, F. D., Wintermeyer, E., Dumig, M. & Frosch, M. Analysis of transcriptional control mechanisms of capsule expression in Neisseria meningitidis. Int. J. Med. Microbiol. 291, 361–369 (2001)

    Article  CAS  Google Scholar 

  15. Johansson, J. et al. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110, 551–561 (2002)

    Article  Google Scholar 

  16. Hoe, N. P. & Goguen, J. D. Temperature sensing in Yersinia pestis: translation of the LcrF activator protein is thermally regulated. J. Bacteriol. 175, 7901–7909 (1993)

    Article  CAS  Google Scholar 

  17. Morita, M., Kanemori, M., Yanagi, H. & Yura, T. Heat-induced synthesis of σ32 in Escherichia coli: structural and functional dissection of rpoH mRNA secondary structure. J. Bacteriol. 181, 401–410 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Böhme, K. et al. Concerted actions of a thermo-labile regulator and a unique intergenic RNA thermosensor control Yersinia virulence. PLoS Pathog. 8, e1002518 (2012)

    Article  Google Scholar 

  19. Kahler, C. M. et al. The (α2→8)-linked polysialic acid capsule and lipooligosaccharide structure both contribute to the ability of serogroup B Neisseria meningitidis to resist the bactericidal activity of normal human serum. Infect. Immun. 66, 5939–5947 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Rameix-Welti, M. A. et al. Influenza A virus neuraminidase enhances meningococcal adhesion to epithelial cells through interaction with sialic acid-containing meningococcal capsules. Infect. Immun. 77, 3588–3595 (2009)

    Article  CAS  Google Scholar 

  21. Lijek, R. S. & Weiser, J. N. Co-infection subverts mucosal immunity in the upper respiratory tract. Curr. Opin. Immunol. 24, 417–423 (2012)

    Article  CAS  Google Scholar 

  22. Cole, P. Recordings of respiratory air temperature. J. Laryngol. Otol. 68, 295–307 (1954)

    Article  CAS  Google Scholar 

  23. Kugelberg, E. et al. The influence of IS1301 in the capsule biosynthesis locus on meningococcal carriage and disease. PLoS ONE 5, e9413 (2010)

    Article  ADS  Google Scholar 

  24. Uria, M. J. et al. A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies. J. Exp. Med. 205, 1423–1434 (2008)

    Article  CAS  Google Scholar 

  25. Miller, J. H. Experiments in Molecular Genetics (Cold Spring Harbour Laboratory Press, 1972)

    Google Scholar 

  26. Chalmers, R. M. & Kleckner, N. IS10/Tn10 transposition efficiently accommodates diverse transposon end configurations. EMBO J. 15, 5112–5122 (1996)

    Article  CAS  Google Scholar 

  27. Johansson, J. et al. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110, 551–561 (2002)

    Article  Google Scholar 

Download references

Acknowledgements

Work in C.M.T.’s laboratory is funded by Programme Grants from the Wellcome Trust and the Medical Research Council, and by the Oxford Martin School. E.L. was supported by an International Postdoctoral fellowship from the Swedish Research Council (Dnr: 524-2010-6726) and E.K. was supported by an EMBO long-term fellowship. We are grateful to J. Johansson, S. Busby and other members of the Tang group for discussions, and to B. Kallipolitis for providing E. coli 30S ribosomes.

Author information

Author notes

  1. Edmund Loh and Elisabeth Kugelberg: These authors contributed equally to this work.

Authors and Affiliations

  1. Sir William Dunn School of Pathology, University of Oxford, Sir Parks Road, Oxford OX1 3RE, UK,

    Edmund Loh, Alexander Tracy & Christoph M. Tang

  2. Centre for Molecular Microbiology and Infection, Imperial College London, London SW7 2AZ, UK,

    Elisabeth Kugelberg, Qian Zhang, Bridget Gollan, Helen Ewles, Vladimir Pelicic & Christoph M. Tang

  3. School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2NR, UK,

    Ronald Chalmers

Authors
  1. Edmund Loh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elisabeth Kugelberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Tracy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bridget Gollan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Helen Ewles
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ronald Chalmers
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vladimir Pelicic
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christoph M. Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

E.L., E.K., A.T., Q.Z., B.G. and H.E. performed the experiments and analysed the data. R.C. and V.P. oversaw the DNA foot-printing and construction of transcription factor mutants. C.M.T. provided overall direction, and wrote the manuscript with input from E.L., E.K. and R.C., and the other authors.

Corresponding author

Correspondence to Christoph M. Tang.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-10 and Supplementary Tables 1-2. (PDF 4042 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loh, E., Kugelberg, E., Tracy, A. et al. Temperature triggers immune evasion by Neisseria meningitidis . Nature 502, 237–240 (2013). https://doi.org/10.1038/nature12616

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature12616

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology