Context-Dependent Roles for Toll-Like Receptors 2 and 9 in the Pathogenesis of Staphylococcus aureus Osteomyelitis

Petronglo, Jenna R.; Putnam, Nicole E.; Ford, Caleb A.; Cruz-Victorio, Virginia; Curry, Jacob M.; Butrico, Casey E.; Fulbright, Laura E.; Johnson, Joshua; Peck, Sun H.; Fatah, Sana R.; Cassat, James E.

doi:10.1128/iai.00417-22

Cited by 3 publications

(2 citation statements)

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“…This effect was not seen for SE planktonic CM which reflects the differences in virulence between SA and SE. Our results are, however, in contrast to a study showing that stimulation of RANKL-primed BMDMs with SA supernatants promotes osteoclastogenesis TLR dependently [ 49 ], indicating that there might also be variations between SA strains.…”

Section: Discussioncontrasting

confidence: 99%

Staphylococci planktonic and biofilm environments differentially affect osteoclast formation

et al. 2023

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Introduction The pathophysiology of chronic implant-related bone infections is characterized by an increase in osteoclast numbers and enhanced bone resorption. Biofilms are a major reason for chronicity of such infections as the biofilm matrix protects bacteria against antibiotics and impairs the function of immune cells. Macrophages are osteoclast precursor cells and therefore linked to inflammation and bone destruction. Objective and method Investigations on the impact of biofilms on the ability of macrophages to form osteoclasts are yet missing and we, therefore, analyzed the effect of Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE) planktonic and biofilm environments on osteoclastogenesis using RAW 264.7 cells and conditioned media (CM). Results Priming with the osteoclastogenic cytokine RANKL before CM addition enabled the cells to differentiate into osteoclasts. This effect was highest in SE planktonic or SA biofilm CM. Simultaneous stimulation with CM and RANKL, however, suppressed osteoclast formation and resulted in formation of inflammation-associated multinucleated giant cells (MGCs) which was most pronounced in SE planktonic CM. Conclusion Our data indicate that the biofilm environment and its high lactate levels are not actively promoting osteoclastogenesis. Hence, the inflammatory immune response against planktonic bacterial factors through Toll-like receptors seems to be the central cause for the pathological osteoclast formation. Therefore, immune stimulation or approaches that aim at biofilm disruption need to consider that this might result in enhanced inflammation-mediated bone destruction.

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Section: Discussioncontrasting

confidence: 99%

Staphylococci planktonic and biofilm environments differentially affect osteoclast formation

et al. 2023

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“…All TLRs but TLR2 and TLR4 are downregulated during osteoclast differentiation, and relative timing of TLR and RANKL/MCSF stimulation of osteoclast precursors elicit opposite effect on osteoclast formation ( 9 ). Very recently it has been reported that TLR2 and TLR9 signaling contributes marginally to the inflammatory bone loss and enhanced osteoclast formation that accompany S. aureus -dependent osteomyelitis (see Osteoclasts and their progenitors ) ( 10 ). However, it is generally accepted that osteoblasts use TLRs and NODs to recognize and respond to S. aureus , which leads to secretion of the master osteoclastogenic cytokine RANKL as well as other factors ( 11 ), as discussed below.…”

Section: Introductionmentioning

confidence: 99%

The osteoblast secretome in Staphylococcus aureus osteomyelitis

et al. 2022

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Osteomyelitis (OM) is an infectious disease of the bone predominantly caused by the opportunistic bacterium Staphylococcus aureus (S. aureus). Typically established upon hematogenous spread of the pathogen to the musculoskeletal system or contamination of the bone after fracture or surgery, osteomyelitis has a complex pathogenesis with a critical involvement of both osteal and immune components. Colonization of the bone by S. aureus is traditionally proposed to induce functional inhibition and/or apoptosis of osteoblasts, alteration of the RANKL/OPG ratio in the bone microenvironment and activation of osteoclasts; all together, these events locally subvert tissue homeostasis causing pathological bone loss. However, this paradigm has been challenged in recent years, in fact osteoblasts are emerging as active players in the induction and orientation of the immune reaction that mounts in the bone during an infection. The interaction with immune cells has been mostly ascribed to osteoblast-derived soluble mediators that add on and synergize with those contributed by professional immune cells. In this respect, several preclinical and clinical observations indicate that osteomyelitis is accompanied by alterations in the local and (sometimes) systemic levels of both pro-inflammatory (e.g., IL-6, IL-1α, TNF-α, IL-1β) and anti-inflammatory (e.g., TGF-β1) cytokines. Here we revisit the role of osteoblasts in bacterial OM, with a focus on their secretome and its crosstalk with cellular and molecular components of the bone microenvironment and immune system.

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Heat-killed Lancefieldella Rimae Induces Bone Resorption by Promoting Osteoclast Differentiation

Park,

Lim,

Park

et al. 2024

Journal of Endodontics

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Context-Dependent Roles for Toll-Like Receptors 2 and 9 in the Pathogenesis of Staphylococcus aureus Osteomyelitis

Abstract: Staphylococcus aureus is the major causative agent of bacterial osteomyelitis, an invasive infection of bone. Inflammation generated by the immune response to S. aureus contributes to bone damage by altering bone homeostasis.

Cited by 3 publications

References 69 publications

Staphylococci planktonic and biofilm environments differentially affect osteoclast formation

Staphylococci planktonic and biofilm environments differentially affect osteoclast formation

The osteoblast secretome in Staphylococcus aureus osteomyelitis

Heat-killed Lancefieldella Rimae Induces Bone Resorption by Promoting Osteoclast Differentiation

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