In vivo internalization of Staphylococcus aureus by embryonic chick osteoblasts

Reilly, Sheila S.; Hudson, Michael; Kellam, James F; Ramp, Warren K.

doi:10.1016/s8756-3282(99)00239-2

Cited by 87 publications

(64 citation statements)

References 32 publications

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“…2A). Nonviable Salmonella cannot invade osteoblasts, and these bone-forming cells have a limited ability to take up bacteria (16,24,47). Therefore, the finding that killed Salmonella could stimulate CXCL10 secretion, albeit at a lower level than the level stimulated by viable bacteria, suggested that osteoblasts might express cell surface molecules which have the ability to sense the presence of gram-negative bacteria or their products.…”

Section: Resultsmentioning

confidence: 99%

Bacterium-Induced CXCL10 Secretion by Osteoblasts Can Be Mediated in Part through Toll-Like Receptor 4

et al. 2002

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Two common pathogens known to cause bone infection, Salmonella and Staphylococcus aureus, were investigated to determine their abilities to induce chemokine expression in cultured mouse and human osteoblasts. While these cells are responsible for bone formation, we were surprised to find that they could respond to bacterial infection by upregulating expression of the chemokine CXCL10 (IP-10). However, there were significant differences in the abilities of the gram-negative bacterium Salmonella and the gram-positive bacterium S. aureus to induce expression of CXCL10. Reverse transcription-PCR and enzyme-linked immunosorbent assay analyses showed high levels of Salmonella-induced CXCL10 mRNA and protein expression, respectively, whereas the osteoblast response to S. aureus was significantly less. Consistent with these findings, Salmonelladerived lipopolysaccharide (LPS), but not S. aureus-derived peptidoglycan, could induce expression of CXCL10. An antibody against toll-like receptor 4 (TLR4) could block the LPS-induced CXCL10 production, demonstrating the functional expression of TLR4 by osteoblasts. Despite the inducible nature of TLR2 mRNA expression by bacterium-infected osteoblasts, peptidoglycan failed to stimulate CXCL10 secretion. Immunofluorescent staining of bacterium-infected calvaria (i.e., skull bone) demonstrated the presence of CXCL10 in osteoblasts. The fact that osteoblasts did not express CXCR3 mRNA, whereas T lymphocytes can express high levels of this receptor, suggests that osteoblast-derived CXCL10 may recruit T lymphocytes to the sites of bone infections.

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Section: Resultsmentioning

confidence: 99%

Bacterium-Induced CXCL10 Secretion by Osteoblasts Can Be Mediated in Part through Toll-Like Receptor 4

et al. 2002

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“…Finally, S. aureus has been shown to invade normal chicken osteoblasts both in vitro and in vivo (15,29). S. aureus cells were found in approximately 14% of calvarial osteoblasts after subcutaneous injection of chicken embryos and in 11% of calvarial and tibial osteoblasts after intra-allantoic injection.…”

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Staphylococcus aureusandSalmonella entericaSerovar Dublin Induce Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Expression by Normal Mouse and Human Osteoblasts

et al. 2001

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Staphylococcus aureus and Salmonella enterica serovar Dublin invade osteoblasts and are causative agents of human bone disease. In the present study, we examined the ability of S. aureus and Salmonella serovar Dublin to induce the production of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by normal osteoblasts. Normal mouse and human osteoblasts were cocultured with S. aureus or Salmonella serovar Dublin at different multiplicities of infection. Following initial incubation and examination of TRAIL expression, extracellular bacteria were killed by the addition of media containing the antibiotic gentamicin. Lysates and conditioned media from osteoblast cultures were then collected at various times following invasion and analyzed. The results demonstrated that S. aureus and Salmonella serovar Dublin are potent inducers of TRAIL expression by osteoblasts. Mouse and human TRAIL mRNA expression was induced by bacterial infection and demonstrated a dose-dependent response. Analysis of kinetics suggested that TRAIL mRNA was induced within 30 min after exposure to bacteria and that its level of expression remained relatively constant over the time period examined. mRNA molecules encoding TRAIL receptors were constitutively expressed by osteoblasts. Furthermore, TRAIL protein was detected as early as 45 min and up to 24 h following infection. The quantity of TRAIL protein produced also increased in a dose-dependent manner. Collectively, these findings suggest a mechanism whereby bacterial pathogens mediate bone destruction via osteoblast apoptosis.

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“…The resultant bone destruction facilitates bacterial invasiveness. S. aureus not only colonizes bone matrix but is internalized in vitro (17,28,29) and in vivo (49) by osteoblasts (bone-forming cells). With the notable exception of Listeria monocytogenes, very little work has been done to examine mechanisms of invasion and intracellular survival by gram-positive bacteria.…”

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Involvement of Mitogen-Activated Protein Kinase Pathways inStaphylococcus aureusInvasion of Normal Osteoblasts

et al. 2001

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Staphylococcus aureus invades osteoblasts and can persist in the intracellular environment. The present study examined the role of osteoblast mitogen-activated protein kinase (MAPK) pathways in bacterial invasion. S. aureus infection of normal human and mouse osteoblasts resulted in an increase in the phosphorylation of the extracellular signal-regulated protein kinases (ERK 1 and 2). This stimulation of ERK 1 and 2 correlated with the time course of S. aureus invasion, and bacterial adherence induced the MAPK pathway. ERK 1 and 2 phosphorylation was time and dose dependent and required active S. aureus gene expression for maximal induction. The nonpathogenic Staphylococcus carnosus was also able to induce ERK 1 and 2 phosphorylation, albeit at lower levels than S. aureus. Phosphorylation of the stress-activated protein kinases was increased in both infected human and mouse osteoblasts; however, the p38 MAPK pathway was not activated in response to S. aureus. Finally, the transcription factor c-Jun, but not Elk-1 or ATF-2, was phosphorylated in response to S. aureus infection.Osteomyelitis (OM) is an infection of bone that results from hematogenous seeding, spread of infection from a contiguous area such as the skin adjacent to a wound, surgical inoculation of bacteria into bone, or trauma coincident with staphylococcal infection (57). The presence of an inert, prosthetic orthopedic device increases the likelihood of disease, and removal of the implant may be required (16). Chronic or recurring OM can be a persistent clinical problem that is difficult to treat effectively and results in abnormal bone remodeling, leading to a vascular compromise in the infected area. Long periods of antibiotic treatment are utilized in an attempt to control OM recurrences; however, methicillin-resistant staphylococci are now commonplace, and therapeutic levels of antibiotics in necrotic bone are difficult to achieve unless antibiotic-impregnated beads or implants are used (9).Staphylococcus aureus is a capable bone pathogen because it possesses several cell surface adhesion molecules that facilitate its binding to the bone matrix. These include fibronectin-binding proteins (18, 30), fibrinogen-binding proteins (6, 10, 36), elastin-binding adhesin (42), collagen-binding adhesin (43), and a broad-specificity adhesin (MAP) which facilitates lowaffinity binding of S. aureus to several proteins, including osteopontin, collagen, bone sialoprotein, fibronectin, fibrinogen, and vitronectin (37). In addition, S. aureus contains surface proteins that are able to stimulate bone resorption (39) via increasing osteoclast activity (4). The resultant bone destruction facilitates bacterial invasiveness. S. aureus not only colonizes bone matrix but is internalized in vitro (17,28,29) and in vivo (49) by osteoblasts (bone-forming cells). With the notable exception of Listeria monocytogenes, very little work has been done to examine mechanisms of invasion and intracellular survival by gram-positive bacteria. The ability of S. aureus to invade osteo...

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In vivo internalization of Staphylococcus aureus by embryonic chick osteoblasts

Cited by 87 publications

References 32 publications

Bacterium-Induced CXCL10 Secretion by Osteoblasts Can Be Mediated in Part through Toll-Like Receptor 4

Bacterium-Induced CXCL10 Secretion by Osteoblasts Can Be Mediated in Part through Toll-Like Receptor 4

Staphylococcus aureusandSalmonella entericaSerovar Dublin Induce Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Expression by Normal Mouse and Human Osteoblasts

Involvement of Mitogen-Activated Protein Kinase Pathways inStaphylococcus aureusInvasion of Normal Osteoblasts

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