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Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity

Claudia Feriotti, Joana Sa-Pessoa, Ricardo Calderón-González, Lili Gu, Brenda Morris, Ryoichi Sugisawa, Jose L. Insua, Michael Carty, Amy Dumigan, Rebecca J. Ingram, Adrien Kisenpfening, Andrew G. Bowie, View ORCID ProfileJosé A. Bengoechea
doi: https://doi.org/10.1101/2021.09.29.462388
Claudia Feriotti
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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Joana Sa-Pessoa
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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Ricardo Calderón-González
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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Lili Gu
2School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
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Brenda Morris
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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Ryoichi Sugisawa
2School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
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Jose L. Insua
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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Michael Carty
2School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
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Amy Dumigan
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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Rebecca J. Ingram
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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Adrien Kisenpfening
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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Andrew G. Bowie
2School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
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José A. Bengoechea
1Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast
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  • ORCID record for José A. Bengoechea
  • For correspondence: j.bengoechea@qub.ac.uk
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SUMMARY

Many bacterial pathogens antagonize host defence responses by translocating effector proteins into cells. It remains an open question how those pathogens not encoding effectors counteract anti-bacterial immunity. Here, we show that Klebsiella pneumoniae hijacks the evolutionary conserved innate immune protein SARM1 to control cell intrinsic immunity. Klebsiella exploits SARM1 to regulate negatively MyD88 and TRIF-governed inflammation, and the activation of the MAP kinases ERK and JNK. SARM1 is required for Klebsiella induction of IL10 by fine-tuning the p38-type I IFN axis. SARM1 inhibits the activation of Klebsiella-induced absent in melanoma 2 inflammasome to limit IL1β production, suppressing further inflammation. Klebsiella exploits type I IFNs to induce SARM1 in a capsule and LPS O-polysaccharide-dependent manner via TLR4-TRAM-TRIF-IRF3-IFNAR1 pathway. Absence of SARM1 reduces the intracellular survival of K. pneumonaie in macrophages whereas sarm1 deficient mice control the infection. Altogether, our results illustrate a hitherto unknown anti-immunology strategy deployed by a human pathogen.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • The authors have declared that no conflict of interest exists.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity
Claudia Feriotti, Joana Sa-Pessoa, Ricardo Calderón-González, Lili Gu, Brenda Morris, Ryoichi Sugisawa, Jose L. Insua, Michael Carty, Amy Dumigan, Rebecca J. Ingram, Adrien Kisenpfening, Andrew G. Bowie, José A. Bengoechea
bioRxiv 2021.09.29.462388; doi: https://doi.org/10.1101/2021.09.29.462388
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Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity
Claudia Feriotti, Joana Sa-Pessoa, Ricardo Calderón-González, Lili Gu, Brenda Morris, Ryoichi Sugisawa, Jose L. Insua, Michael Carty, Amy Dumigan, Rebecca J. Ingram, Adrien Kisenpfening, Andrew G. Bowie, José A. Bengoechea
bioRxiv 2021.09.29.462388; doi: https://doi.org/10.1101/2021.09.29.462388

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