Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

Abstract

There is limited knowledge about host factors that facilitate eradication of Staphylococcus aureus infection in the lung. Methicillin-resistant S. aureus has remained a major cause of hospital-and health care-associated pneumonia since its appearance over 40 years ago and has recently become a more prominent etiology in community acquired pneumonia. Colonization of nasal epithelium with S. aureus, a normal occurrence in over 20% of the population, increases the risk for the development of staphylococcal pneumonia (1). Furthermore, S. aureus co-infections are a major complication contributing to high morbidity and mortality during both pandemic and seasonal influenza virus pneumonia (2). S. aureus deploys a combination of virulence factors, including adhesins, toxins, and immunomodulatory molecules, that facilitate infection of different host tissues (3, 4).Surfactant protein A (SP-A) 3 is a crucial component of the pulmonary innate immune system in the alveolar spaces (5, 6). SP-A is the major protein constituent of pulmonary surfactant; it is involved in organization of large aggregate surfactant phospholipids lining the alveolar surface and acts as an opsonin for pathogens (7). SP-A is incorporated in the tubular myelin fraction of pulmonary surfactant that covers the alveolar lining fluid of the distal airway epithelium. The presence of pathogen-derived molecules may trigger reorganization of surfactant lipids (8 -11) and exposure of SP-A to bind pathogens at points of entry on the surfactant interface. Alveolar macrophages in the aqueous hypophase may then patrol areas of disturbance on the surfactant layer binding SP-A-opsonized bacteria. SP-A binds pathogens via a carboxyl-terminal carbohydrate recognition domain in a calcium-dependent manner. Amino-terminal collagen-like and coiled-coil do-

BDCA1-Positive Dendritic Cells (DCs) Represent a Unique Human Myeloid DC Subset That Induces Innate and Adaptive Immune Responses to Staphylococcus aureus Infection

“…The function of SR-A in human and mouse DCs and macrophages in response to Gram-negative and Gram-positive bacteria has been investigated, showing that SR-A functionally contributes to phagocytosis of those bacteria (37,38). Moreover, many studies showed that SR-A plays a significant role in the phagocytosis of S. aureus (39)(40)(41). We found that the presence of both SR-A and TLR-2 is required for the optimal phagocytosis of S. aureus by BDCA1 ϩ mDCs.…”

GM-CSF modulates pulmonary resistance to influenza A infection

“…GM-CSF enhances expression of scavenger receptors SR-A and MARCO (Sulahian et al, 2008; Szeliga et al, 2008) which may modify host resistance to viral infection (DeWitte-Orr et al, 2010; Mukhopadhyay et al, 2011). SR-A modifies inflammatory responses via the SP-A receptor SP-R210 (Sever-Chroneos et al, 2011). Mean survival from influenza infection between SR-A −/− and WT mice were similar (Fig.…”

“…Alveolar macrophages isolated by lung lavage were processed, stained, and analyzed by flow cytometry as described in detail previously (Sever-Chroneos et al, 2011). Briefly, cells were stained with monoclonal PE/Cy5-conjugated CD11c antibody clone N418 (eBiosciences, San Diego, CA), rabbit polyclonal SP-R210/Myo18A antibody (Protein-Tech, Chicago, IL), and a goat polyclonal anti-SR-A/Msr1 antibody (R&D Systems, Minneapolis, MN).…”

A TLR4-interacting SPA4 peptide inhibits LPS-induced lung inflammation

“…The arrows within the photomicrograph indicate nuclear localization of NF-kB-p65. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] regions of SP-A that bind to TLR4 and modulate immune responses.…”