Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26934588
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Human Monocyte-Derived Osteoclasts Are Targeted by Staphylococcal Pore-Forming
Toxins and Superantigens
#MMPMID26934588
Flammier S
; Rasigade JP
; Badiou C
; Henry T
; Vandenesch F
; Laurent F
; Trouillet-Assant S
PLoS One
2016[]; 11
(3
): e0150693
PMID26934588
show ga
Staphylococcus aureus is the leading cause of bone and joint infections (BJIs).
Staphylococcal pathogenesis involves numerous virulence factors including
secreted toxins such as pore-forming toxins (PFTs) and superantigens. The role of
these toxins on BJI outcome is largely unknown. In particular, few studies have
examined how osteoclasts, the bone-resorbing cells, respond to exposure to
staphylococcal PFTs and superantigens. We investigated the direct impact of
recombinant staphylococcal toxins on human primary mature monocyte-derived
osteoclasts, in terms of cytotoxicity and cell activation with cell death and
bone resorption assays, using macrophages of the corresponding donors as a
reference. Monocyte-derived osteoclasts displayed similar toxin susceptibility
profiles compared to macrophages. Specifically, we demonstrated that the
Panton-Valentine leukocidin, known as one of the most powerful PFT which lyses
myeloid cells after binding to the C5a receptor, was able to induce the death of
osteoclasts. The archetypal superantigen TSST-1 was not cytotoxic but enhanced
the bone resorption activity of osteoclasts, suggesting a novel mechanism by
which superantigen-producing S. aureus can accelerate the destruction of bone
tissue during BJI. Altogether, our data indicate that the diverse clinical
presentations of BJIs could be related, at least partly, to the toxin profiles of
S. aureus isolates involved in these severe infections.
free
free
free
