1887

Abstract

Osteoblasts produce an array of immune molecules following bacterial challenge that can contribute to inflammation and the recruitment of leukocytes to sites of infection during bone diseases such as osteomyelitis. However, the mechanisms by which osteoblasts perceive and respond to facultative intracellular pathogens such as species and have not been determined. Recently, our laboratory has described the expression in osteoblasts of members of the nucleotide-binding domain leucine-rich repeat region containing family of proteins that include nucleotide-binding oligomerization domain-2 (NOD2), a molecule that functions as an intracellular receptor for bacterial peptidoglycans. In the present study, we demonstrate that NOD2 expression is required for select inflammatory mediator production by osteoblasts following infection with the invasive pathogen . In contrast, we have found that the inflammatory immune responses of osteoblasts to the passively internalized bacterial species , heat-killed pathogenic , a non-invasive strain and specific Toll-like receptor ligands are not reduced in the absence of NOD2 expression but are, in fact, elevated. Based upon these findings, we suggest that NOD2 serves differential roles in osteoblasts, promoting inflammatory responses to invasive bacteria while tempering cell responses to extracellular and/or passively internalized bacterial species.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.015859-0
2010-07-01
2024-12-07
Loading full text...

Full text loading...

/deliver/fulltext/jmm/59/7/755.html?itemId=/content/journal/jmm/10.1099/jmm.0.015859-0&mimeType=html&fmt=ahah

References

  1. Barnich N., Hisamatsu T., Aguirre J. E., Xavier R., Reinecker H. C., Podolsky D. K. 2005; GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. J Biol Chem 280:19021–19026 [CrossRef]
    [Google Scholar]
  2. Bost K. L., Ramp W. K., Nicholson N. C., Bento J. L., Marriott I., Hudson M. C. 1999; Staphylococcus aureus infection of mouse or human osteoblasts induces high levels of interleukin-6 and interleukin-12 production. J Infect Dis 180:1912–1920 [CrossRef]
    [Google Scholar]
  3. Bost K. L., Bento J. L., Ellington J. K., Marriott I., Hudson M. C. 2000; Induction of colony-stimulating factor expression following Staphylococcus or Salmonella interaction with mouse or human osteoblasts. Infect Immun 68:5075–5083 [CrossRef]
    [Google Scholar]
  4. Bost K. L., Bento J. L., Petty C. C., Schrum L. W., Hudson M. C., Marriott I. 2001; Monocyte chemoattractant protein-1 expression by osteoblasts following infection with Staphylococcus aureus or Salmonella . J Interferon Cytokine Res 21:297–304 [CrossRef]
    [Google Scholar]
  5. Chin A. I., Dempsey P. W., Bruhn K., Miller J. F., Xu Y., Cheng G. 2002; Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature 416:190–194 [CrossRef]
    [Google Scholar]
  6. Ellington J. K., Reilly S. S., Ramp W. K., Smeltzer M. S., Kellam J. F., Hudson M. C. 1999; Mechanisms of Staphylococcus aureus invasion of cultured osteoblasts. Microb Pathog 26:317–323 [CrossRef]
    [Google Scholar]
  7. Gasper N. A., Petty C. C., Schrum L. W., Marriott I., Bost K. L. 2002; Bacterium-induced CXCL10 secretion by osteoblasts can be mediated in part through toll-like receptor 4. Infect Immun 70:4075–4082 [CrossRef]
    [Google Scholar]
  8. Girardin S. E., Boneca I. G., Viala J., Chamaillard M., Labigne A., Thomas G., Philpott D. J., Sansonetti P. J. 2003; Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278:8869–8872 [CrossRef]
    [Google Scholar]
  9. Inohara N., Ogura Y., Fontalba A., Gutierrez O., Pons F., Crespo J., Fukase K., Inamura S., Kusumoto S. other authors 2003; Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem 278:5509–5512 [CrossRef]
    [Google Scholar]
  10. Joosten L. A., Heinhuis B., Abdollahi-Roodsaz S., Ferwerda G., Lebourhis L., Philpott D. J., Nahori M. A., Popa C., Morre S. A. & other authors ; 2008 Differential function of the NACHT-LRR (NLR) members Nod1 and Nod2 in arthritis. Proc Natl Acad Sci U S A 1059017–9022 [CrossRef]
    [Google Scholar]
  11. Kikuchi T., Matsuguchi T., Tsuboi N., Mitani A., Tanaka S., Matsuoka M., Yamamoto G., Hishikawa T., Noguchi T., Yoshikai Y. 2001; Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors. J Immunol 166:3574–3579 [CrossRef]
    [Google Scholar]
  12. Kobayashi K., Inohara N., Hernandez L. D., Galan J. E., Nunez G., Janeway C. A., Medzhitov R., Flavell R. A. 2002; RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416:194–199 [CrossRef]
    [Google Scholar]
  13. Kobayashi K. S., Chamaillard M., Ogura Y., Henegariu O., Inohara N., Nuñez G., Flavell R. A. 2005; Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731–734 [CrossRef]
    [Google Scholar]
  14. Leber J. H., Crimmins G. T., Raghavan S., Meyer-Morse N. P., Cox J. S., Portnoy D. A. 2008; Distinct TLR- and NLR-mediated transcriptional responses to an intracellular pathogen. PLoS Pathog 4:e6 [CrossRef]
    [Google Scholar]
  15. Madrazo D. R., Tranguch S. L., Marriott I. 2003; Signaling via Toll-like receptor 5 can initiate inflammatory mediator production by murine osteoblasts. Infect Immun 71:5418–5421 [CrossRef]
    [Google Scholar]
  16. Marriott I. 2004; Osteoblast responses to bacterial pathogens: a previously unappreciated role for bone-forming cells in host defense and disease progression. Immunol Res 30:291–308 [CrossRef]
    [Google Scholar]
  17. Marriott I., Rati D. M., McCall S. H., Tranguch S. L. 2005; Induction of Nod1 and Nod2 intracellular pattern recognition receptors in murine osteoblasts following bacterial challenge. Infect Immun 73:2967–2973 [CrossRef]
    [Google Scholar]
  18. Marriott I., Miller J. R., Sahraei M. 2007; Therapeutic strategies against inflammation and bone loss associated with osteomyelitis. Curr Opin Investig Drugs 8:887–898
    [Google Scholar]
  19. McCall S. H., Sahraei M., Young A. B., Worley C. S., Duncan J. A., Ting J. P., Marriott I. 2008; Osteoblasts express NLRP3, a nucleotide-binding domain and leucine-rich repeat region containing receptor implicated in bacterially induced cell death. J Bone Miner Res 23:30–40
    [Google Scholar]
  20. Nemoto E., Honda T., Kanaya S., Takada H., Shimauchi H. 2008; Expression of functional Toll-like receptors and nucleotide-binding oligomerization domain proteins in murine cementoblasts and their upregulation during cell differentiation. J Periodontal Res 43:585–593 [CrossRef]
    [Google Scholar]
  21. Netea M. G., Ferwerda G., de Jong D. J., Jansen T., Jacobs L., Kramer M., Naber T. H., Drenth J. P., Girardin S. E. other authors 2005; Nucleotide-binding oligomerization domain-2 modulates specific TLR pathways for the induction of cytokine release. J Immunol 174:6518–6523 [CrossRef]
    [Google Scholar]
  22. Ohl M. E., Miller S. I. 2001; Salmonella: a model for bacterial pathogenesis. Annu Rev Med 52:259–274 [CrossRef]
    [Google Scholar]
  23. Reott M. A. Jr, Ritchie-Miller S. L., Anguita J., Hudson M. C. 2008; TRAIL expression is induced in both osteoblasts containing intracellular Staphylococcus aureus and uninfected osteoblasts in infected cultures. FEMS Microbiol Lett 278:185–192 [CrossRef]
    [Google Scholar]
  24. Schrum L. W., Bost K. L., Hudson M. C., Marriott I. 2003; Bacterial infection induces expression of functional MHC class II molecules in murine and human osteoblasts. Bone 33:812–821 [CrossRef]
    [Google Scholar]
  25. Strober W., Murray P. J., Kitani A., Watanabe T. 2006; Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol 6:9–20 [CrossRef]
    [Google Scholar]
  26. Sweet M. J., Campbell C. C., Sester D. P., Xu D., McDonald R. C., Stacey K. J., Hume D. A., Liew F. Y. 2002; Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages. J Immunol 168:392–399 [CrossRef]
    [Google Scholar]
  27. Ting J. P., Davis B. K. 2005; CATERPILLER: a novel gene family important in immunity, cell death, and diseases. Annu Rev Immunol 23:387–414 [CrossRef]
    [Google Scholar]
  28. Yang S., Takahashi N., Yamashita T., Sato N., Takahashi M., Mogi M., Uematsu T., Kobayashi Y., Nakamichi Y. other authors 2005; Muramyl dipeptide enhances osteoclast formation induced by lipopolysaccharide, IL-1 alpha, and TNF-alpha through nucleotide-binding oligomerization domain 2-mediated signaling in osteoblasts. J Immunol 175:1956–1964 [CrossRef]
    [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.015859-0
Loading
/content/journal/jmm/10.1099/jmm.0.015859-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error