INVESTIGADORES
SORDELLI Daniel Oscar
artículos
Título:
Shedding of TNFR1 induced by protein A decreases TNF-α availability and inflammation during systemic Staphylococcus aureus infection.
Autor/es:
GIAI C; GONZALEZ C; LEDO C; GAROFALO A; DI GENARO MS; SORDELLI DO; GOMEZ MI
Revista:
INFECTION AND IMMUNITY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Lugar: Washington; Año: 2013 vol. 81 p. 4200 - 4207
ISSN:
0019-9567
Resumen:
Staphylococcus aureus infections are an important public health concern
due to their increasing incidence and high rates of mortality. The
success of S. aureus as a pathogen is highly related to its enormous
capacity to evade the host immune response. The critical role of tumor
necrosis factor alpha (TNF-α) in the initial host defense against
systemic staphylococcal infection has been demonstrated in experimental
models and may partially explain the lack of significant benefits
observed in clinical trials attempting to neutralize this cytokine in
septic patients. S. aureus protein A plays a key role in regulating
inflammation through its ability to bind and signal through the TNF-α
receptor 1 (TNFR1). In this study, we demonstrate that S. aureus, via
protein A-mediated signaling, induces early shedding of TNFR1, which
precedes the secretion of TNF-α in vitro and in vivo. The results
obtained using a protein A-deficient mutant and tnfr1(-/-) mice strongly
suggest that the increased levels of soluble TNFR1 present during
experimental S. aureus infection may neutralize circulating TNF-α and
impair the host inflammatory response. Early shedding of TNFR1 induced
by protein A may constitute a novel mechanism by which S. aureus
subverts the host immune response.