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Mucosal innate response stimulation induced by lipopolysaccharide protects against Bordetella pertussis colonization

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Abstract

Non-specific enhancement of the airways innate response has been shown to impair lung infections in several models of infection such diverse as influenza A, Streptococcus pneumoniae, and Aspergillus niger. Our aim was to evaluate whether a similar event could operate in the context of Bordetella pertussis respiratory infection, not only to enrich the knowledge of host–bacteria interaction but also to establish immunological basis for the development of new control strategies against the pathogen. Using a B. pertussis intranasal infection model and coadministration of different TLR agonists at the moment of the infection, we observed that the enhancement of innate response activation, in a TLR4-dependent way, could efficiently impair B. pertussis colonization (P < 0.001). While LPS from different microbial sources were equally effective in promoting this effect, flagellin and poly I:C coadministration, in spite of inducing expression of innate response markers TNFα, CXCL2, CXCL10 and IL6, was not effective to prevent B. pertussis colonization. Our results indicate that during the early stage of infection, specific anti-microbial mechanisms triggered by TLR4 stimulation are able to impair B. pertussis colonization. These findings could complement our current view of the role of TLR4-dependent processes that contribute to anti-pertussis immunity.

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References

  1. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511

    Article  CAS  PubMed  Google Scholar 

  2. Banus HA, van Kranen HJ, Mooi FR, Hoebee B, Nagelkerke NJ, Demant P, Kimman TG (2005) Genetic control of Bordetella pertussis infection: identification of susceptibility loci using recombinant congenic strains of mice. Infect Immun 73:741–747

    Article  CAS  PubMed  Google Scholar 

  3. Banus HA, Vandebriel RJ, de Ruiter H, Dormans JA, Nagelkerke NJ, Mooi FR, Hoebee B, van Kranen HJ, Kimman TG (2006) Host genetics of Bordetella pertussis infection in mice: significance of toll-like receptor 4 in genetic susceptibility and pathobiology. Infect Immun 74:2596–2605

    Article  CAS  PubMed  Google Scholar 

  4. Carbonetti NH (2007) Immunomodulation in the pathogenesis of Bordetella pertussis infection and disease. Curr Opin Pharmacol 7:272–278

    Article  CAS  PubMed  Google Scholar 

  5. Carbonetti NH, Artamonova GV, Andreasen C, Bushar N (2005) Pertussis toxin and adenylate cyclase toxin provide a one-two punch for establishment of Bordetella pertussis infection of the respiratory tract. Infect Immun 73:2698–2703

    Article  CAS  PubMed  Google Scholar 

  6. Clement CG, Evans SE, Evans CM, Hawke D, Kobayashi R, Reynolds PR, Moghaddam SJ, Scott BL, Melicoff E, Adachi R, Dickey BF, Tuvim MJ (2008) Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice. Am J Respir Crit Care Med 177:1322–1330

    Article  PubMed  Google Scholar 

  7. Didierlaurent A, Goulding J, Patel S, Snelgrove R, Low L, Bebien M, Lawrence T, van Rijt LS, Lambrecht BN, Sirard JC, Hussell T (2008) Sustained desensitization to bacterial toll-like receptor ligands after resolution of respiratory influenza infection. J Exp Med 205:323–329

    Article  CAS  PubMed  Google Scholar 

  8. Evans SE, Scott BL, Clement CG, Larson DT, Kontoyiannis D, Lewis RE, Lasala PR, Pawlik J, Peterson JW, Chopra AK, Klimpel G, Bowden G, Hook M, Xu Y, Tuvim MJ, Dickey BF (2009) Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi. Am J Respir Cell Mol Biol 27:27

    Google Scholar 

  9. He Q, Mertsola J (2008) Factors contributing to pertussis resurgence. Future Microbiol 3:329–339

    Article  PubMed  Google Scholar 

  10. Higgins SC, Jarnicki AG, Lavelle EC, Mills KH (2006) TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. J Immunol 177:7980–7989

    CAS  PubMed  Google Scholar 

  11. Higgins SC, Lavelle EC, McCann C, Keogh B, McNeela E, Byrne P, O’Gorman B, Jarnicki A, McGuirk P, Mills KH (2003) Toll-like receptor 4-mediated innate IL-10 activates antigen-specific regulatory T cells and confers resistance to Bordetella pertussis by inhibiting inflammatory pathology. J Immunol 171:3119–3127

    CAS  PubMed  Google Scholar 

  12. Hozbor D, Rodriguez ME, Samo A, Lagares A, Yantorno O (1993) Release of lipopolysaccharide during Bordetella pertussis growth. Res Microbiol 144:201–209

    Article  CAS  PubMed  Google Scholar 

  13. Kawai T, Akira S (2007) TLR signaling. Semin Immunol 19:24–32

    Article  CAS  PubMed  Google Scholar 

  14. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  15. Mayer AK, Muehmer M, Mages J, Gueinzius K, Hess C, Heeg K, Bals R, Lang R, Dalpke AH (2007) Differential recognition of TLR-dependent microbial ligands in human bronchial epithelial cells. J Immunol 178:3134–3142

    CAS  PubMed  Google Scholar 

  16. Mooi FR, He Q, Guiso N (2007) Phylogeny, evolution, and epidemiology of bordetellae. Horizon Scientific Press

  17. Roberts R, Moreno G, Bottero D, Gaillard ME, Fingermann M, Graieb A, Rumbo M, Hozbor D (2008) Outer membrane vesicles as acellular vaccine against pertussis. Vaccine 26:4639–4646

    Article  CAS  PubMed  Google Scholar 

  18. Raoust E, Balloy V, Garcia-Verdugo I, Touqui L, Ramphal R, Chignard M (2009) Pseudomonas aeruginosa LPS or flagellin are sufficient to activate TLR-dependent signaling in murine alveolar macrophages and airway epithelial cells. PLoS One 6 (4): e7259

  19. Rumbo M, Sierro F, Debard N, Kraehenbuhl JP, Finke D (2004) Lymphotoxin beta receptor signaling induces the chemokine CCL20 in intestinal epithelium. Gastroenterology 127:213–223

    Article  CAS  PubMed  Google Scholar 

  20. Sierro F, Dubois B, Coste A, Kaiserlian D, Kraehenbuhl JP, Sirard JC (2001) Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells. Proc Natl Acad Sci USA 98:13722–13727

    Article  CAS  PubMed  Google Scholar 

  21. Sintchenko V (2008) The re-emergence of pertussis: implications for diagnosis and surveillance. N S W Public Health Bull 19:143–145

    PubMed  Google Scholar 

  22. Tuvim MJ, Evans SE, Clement CG, Dickey BF, Gilbert BE (2009) Augmented lung inflammation protects against influenza A pneumonia. PLoS One 4:4176

    Article  Google Scholar 

  23. Ueno K, Koga T, Kato K, Golenbock D, Gendler S, Kai H, Kim K (2008) MUC1 mucin is a negative regulator of toll-like receptor signaling. Am J Respir Cell Mol Biol 38:263–268

    Article  CAS  PubMed  Google Scholar 

  24. West NP, Jungnitz H, Fitter JT, McArthur JD, Guzman CA, Walker MJ (2000) Role of phosphoglucomutase of Bordetella bronchiseptica in lipopolysaccharide biosynthesis and virulence. Infect Immun 68:4673–4680

    Article  CAS  PubMed  Google Scholar 

  25. Wong JP, Christopher ME, Viswanathan S, Karpoff N, Dai X, Das D, Sun LQ, Wang M, Salazar AM (2009) Activation of toll-like receptor signaling pathway for protection against influenza virus infection. Vaccine 27:3481–3483

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by EU INCO 032296, ANCPyT (Argentina) grants to DH and MR and CICBA grant to DH. DH is a member of the Scientific Career of CICBA. MR, FS and JF are members of the Scientific Career of CONICET. AE and GM have fellowships from ANPCyT.

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Correspondence to Daniela Flavia Hozbor.

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Errea, A., Moreno, G., Sisti, F. et al. Mucosal innate response stimulation induced by lipopolysaccharide protects against Bordetella pertussis colonization. Med Microbiol Immunol 199, 103–108 (2010). https://doi.org/10.1007/s00430-010-0142-5

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  • DOI: https://doi.org/10.1007/s00430-010-0142-5

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