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Translation inhibition and metabolic stress pathways in the host response to bacterial pathogens

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Abstract

Activation of most major innate immune signalling cascades relies on the detection of microorganisms or their associated danger signals by host pattern recognition molecules. A flurry of recent studies has now uncovered a role for host translation inhibition in innate immune surveillance and the detection of bacterial pathogens. Here, we present the main findings from these studies and discuss whether translation inhibition is an alarm signal that directly drives innate immune responses to bacterial pathogens, or rather one component of a more general metabolic stress response to infection.

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Figure 1: Translation inhibition by bacterial pathogens.
Figure 2: Translation inhibition in the context of host defence against bacterial pathogens.

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References

  1. Kumar, H., Kawai, T. & Akira, S. Pathogen recognition in the innate immune response. Biochem. J. 420, 1–16 (2009).

    Article  CAS  Google Scholar 

  2. Fritz, J. H., Ferrero, R. L., Philpott, D. J. & Girardin, S. E. Nod-like proteins in immunity, inflammation and disease. Nature Immunol. 7, 1250–1257 (2006).

    Article  CAS  Google Scholar 

  3. Tanji, T. & Ip, Y. T. Regulators of the Toll and Imd pathways in the Drosophila innate immune response. Trends Immunol. 26, 193–198 (2005).

    Article  CAS  Google Scholar 

  4. Takeuchi, O. & Akira, S. Pattern recognition receptors and inflammation. Cell 140, 805–820 (2010).

    Article  CAS  Google Scholar 

  5. Pedra, J. H., Cassel, S. L. & Sutterwala, F. S. Sensing pathogens and danger signals by the inflammasome. Curr. Opin. Immunol. 21, 10–16 (2009).

    Article  CAS  Google Scholar 

  6. Benko, S., Philpott, D. J. & Girardin, S. E. The microbial and danger signals that activate Nod-like receptors. Cytokine 43, 368–373 (2008).

    Article  CAS  Google Scholar 

  7. Bonardi, V. & Dangl, J. L. How complex are intracellular immune receptor signaling complexes? Front. Plant Sci. 3, 237 (2012).

    Article  Google Scholar 

  8. Chakrabarti, S., Liehl, P., Buchon, N. & Lemaitre, B. Infection-induced host translational blockage inhibits immune responses and epithelial renewal in the Drosophila gut. Cell Host Microbe 12, 60–70 (2012).

    Article  CAS  Google Scholar 

  9. Dunbar, T. L., Yan, Z., Balla, K. M., Smelkinson, M. G. & Troemel, E. R. C. elegans detects pathogen-induced translational inhibition to activate immune signaling. Cell Host Microbe 11, 375–386 (2012).

    Article  CAS  Google Scholar 

  10. Fontana, M. F. et al. Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila. PLoS Pathog. 7, e1001289 (2011).

    Article  CAS  Google Scholar 

  11. Fontana, M. F., Shin, S. & Vance, R. E. Activation of host mitogen-activated protein kinases by secreted Legionella pneumophila effectors that inhibit host protein translation. Infect. Immun. 80, 3570–3575 (2012).

    Article  CAS  Google Scholar 

  12. McEwan, D. L., Kirienko, N. V. & Ausubel, F. M. Host translational inhibition by Pseudomonas aeruginosa exotoxin A triggers an immune response in Caenorhabditis elegans. Cell Host Microbe 11, 364–374 (2012).

    Article  CAS  Google Scholar 

  13. Melo, J. A. & Ruvkun, G. Inactivation of conserved C. elegans genes engages pathogen- and xenobiotic-associated defenses. Cell 149, 452–466 (2012).

    Article  CAS  Google Scholar 

  14. Tattoli, I. et al. Amino acid starvation induced by invasive bacterial pathogens triggers an innate host defense program. Cell Host Microbe 11, 563–575 (2012).

    Article  CAS  Google Scholar 

  15. Mohr, I. & Sonenberg, N. Host translation at the nexus of infection and immunity. Cell Host Microbe 12, 470–483 (2012).

    Article  CAS  Google Scholar 

  16. Luo, Z.-Q. Legionella secreted effectors and innate immune responses. Cell. Microbiol. 14, 19–27 (2012).

    Article  Google Scholar 

  17. Hubber, A. & Roy, C. R. Modulation of host cell function by Legionella pneumophila type IV effectors. Annu. Rev. Cell Dev. Biol. 26, 261–283 (2010).

    Article  CAS  Google Scholar 

  18. Estes, K. A., Dunbar, T. L., Powell, J. R., Ausubel, F. M. & Troemel, E. R. bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 107, 2153–2158 (2010).

    Article  CAS  Google Scholar 

  19. Vattem, K. M. & Wek, R. C. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc. Natl Acad. Sci. USA 101, 11269–11274 (2004).

    Article  CAS  Google Scholar 

  20. Buchon, N., Broderick, N. A., Poidevin, M., Pradervand, S. & Lemaitre, B. Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. Cell Host Microbe 5, 200–211 (2009).

    Article  CAS  Google Scholar 

  21. Buchon, N., Broderick, N. A., Kuraishi, T. & Lemaitre, B. Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol. 8, 152 (2010).

    Article  CAS  Google Scholar 

  22. Kloft, N. et al. Pro-autophagic signal induction by bacterial pore-forming toxins. Med. Microbiol. Immunol. 199, 299–309 (2010).

    Article  CAS  Google Scholar 

  23. Kloft, N. et al. A subunit of eukaryotic translation initiation factor 2α–phosphatase (CreP/PPP1R15B) regulates membrane traffic. J. Biol. Chem. 287, 35299–35317 (2012).

    Article  CAS  Google Scholar 

  24. Tattoli, I., Philpott, D. J. & Girardin, S. E. The bacterial and cellular determinants controlling the recruitment of mTOR to the Salmonella-containing vacuole. Biol. Open 1, 1215–1225 (2012).

    Article  CAS  Google Scholar 

  25. Gonzalez, M. R. et al. Pore-forming toxins induce multiple cellular responses promoting survival. Cell. Microbiol. 13, 1026–1043 (2011).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank E. R. Troemel and D. J. Philpott for critical reading of the manuscript. Research in the B.L. laboratory is supported by grants from the European Research Council and by the Swiss National Science Foundation (grant 3100A0-12079/1). Research in the S.E.G. laboratory is supported by grants from the Canadian Institutes of Health Research, the Burroughs Wellcome Fund and the Crohn's and Colitis Foundation of Canada.

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Correspondence to Bruno Lemaitre or Stephen E. Girardin.

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Lemaitre, B., Girardin, S. Translation inhibition and metabolic stress pathways in the host response to bacterial pathogens. Nat Rev Microbiol 11, 365–369 (2013). https://doi.org/10.1038/nrmicro3029

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