Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1

NATURE MEDICINE, VOLUME 10, 842~848, 2004

Speaker: 陳澤思                                 Date: 2004/11/10 13:00~14:00

Commentator: 楊倍昌 老師                            Place:Room 601

Abstract:

  Staphylococcus aureus (S. aureus), a major cause of pulmonary infection, is associated with primary pneumonia in infants, young children and secondary pneumonia following viral infection and is one of the most common causes of hospital-acquired pneumonia.  It also frequently contributes to airway disease in patients with cystic fibrosis.¹  Because protein A is a major surface protein present in almost all strains of S. aureus, especially respiratory isolates, the authors considered that it is likely to have a specific role in pulmonary infection. The widespread distribution of TNFR1 and its accessibility on the surface of the respiratory epithelium make it an attractive candidate for mediating the host response to staphylococci in the airway.  In this study, they focus on the role of protein A-TNFR1 signaling in the airway and its relevance to the pathogenesis of staphylococcal pneumonia.²  In cystic fibrosis, defective sialylation results in increased numbers of epithelial receptor sites and increased IL-8 production induced by adherent bacteria.  Although the airway epithelial response to infection seems appropriate in the normal host, it may be useful to modulate components of this signaling cascade in specific pathological conditions such as CF, to prevent undesirable consequences of excessive inflammation in the lung.³

References:

(1) Heyer G. et al. Staphylococcus aureus agr and sarA functions are required for invasive infection but not inflammatory responses in the lung. Infection and Immunity, 70, 127-133 (2002)

(2) Gomez, M.I. et al. Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nature Medicine, 10, 842-848(2004)

(3) Ratner, A.J. et al. Cystic fibrosis pathogens activate Ca²⁺-dependent mitogen-activated protein kinase signaling pathways in airway epithelial cells. The journal of biological chemistry, 276,19267-19275(2001)