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Infection and Immunity, March 2003, p. 1209-1216, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1209-1216.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Functional CD40 Expression Induced following Bacterial Infection of Mouse and Human Osteoblasts

Laura W. Schrum,1* Ian Marriott,1 Betsy R. Butler,1,2 Elaine K. Thomas,3 Michael C. Hudson,1 and Kenneth L. Bost1

Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223,1 Department of Natural Sciences, Johnson C. Smith University, Charlotte, North Carolina 28216,2 Immunex Corporation, Seattle, Washington 981013

Received 19 July 2002/ Returned for modification 30 September 2002/ Accepted 4 December 2002

Bacterially induced bone infections often result in significant local inflammatory responses which are coupled with loss of bone. However, the mechanisms necessary for the protective host response, or those responsible for pathogen-induced bone loss, are not clear. Recent evidence demonstrates that bacterially infected osteoblasts secrete chemokines and cytokines, suggesting that these cells may have an unappreciated role in supporting localized inflammation. In this study, mouse and human osteoblasts were investigated for their ability to express functional CD40 upon exposure to two important pathogens of bone, Staphylococcus aureus and Salmonella enterica serovar Dublin. Bacterial infection of cultured mouse or human osteoblasts resulted in increased CD40 mRNA and CD40 protein expression induced by either pathogen. Importantly, CD40 expression by osteoblasts was functional, as assessed by ligation of this molecule with recombinant, soluble CD154. CD40 activity was assessed by induction of interleukin-6 and granulocyte-macrophage colony-stimulating factor in osteoblasts following ligation. Cocultures of activated CD4+ T lymphocytes and osteoblasts could interact via CD40 and CD154, since an antibody against CD40 could block macrophage inflammatory protein-1{alpha} secretion. Taken together, these studies conclusively demonstrate that infected osteoblasts can upregulate expression of functional CD40 molecules which mediate cytokine secretion. This surprising result further supports the notion that bone-forming osteoblasts can directly interact with CD154-expressing cells (i.e., T lymphocytes) and can contribute to the host response during bone infection.

* Corresponding author. Mailing address: Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223. Phone: (704) 687-4897. Fax: (704) 687-3128. E-mail: lwschrum{at}email.uncc.edu.

Editor: J. T. Barbieri

Infection and Immunity, March 2003, p. 1209-1216, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1209-1216.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bosse, M. J., Gruber, H. E., Ramp, W. K. (2005). Internalization of Bacteria by Osteoblasts in a Patient with Recurrent, Long-Term Osteomyelitis. A Case Report. JBJS 87: 1343-1347 [Full Text]  
  • 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 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  


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