TY - JOUR
T1 - 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
AU - Sever-Chroneos, Zvjezdana
AU - Krupa, Agnieszka
AU - Davis, Jeremy
AU - Hasan, Misbah
AU - Yang, Ching Hui
AU - Szeliga, Jacek
AU - Herrmann, Mathias
AU - Hussain, Muzafar
AU - Geisbrecht, Brian V.
AU - Kobzik, Lester
AU - Chroneos, Zissis C.
PY - 2011/2/11
Y1 - 2011/2/11
N2 - Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap+) but not Eap-deficient (Eap -) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap+ S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly,WTmice cleared infection with Eap+ but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap+ S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap- S. aureus was impaired. Macrophages express two isoforms: SP-R210L and SP-R210S. The results show that WT alveolar macrophages are distinguished by expression of SP-R210L, whereas SR-A-/- alveolar macrophages are deficient in SP-R210L expressing only SP-R210S. Accordingly, SR-A-/- mice were highly susceptible to both Eap+ and Eap- S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210L mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A.
AB - Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap+) but not Eap-deficient (Eap -) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap+ S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly,WTmice cleared infection with Eap+ but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap+ S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap- S. aureus was impaired. Macrophages express two isoforms: SP-R210L and SP-R210S. The results show that WT alveolar macrophages are distinguished by expression of SP-R210L, whereas SR-A-/- alveolar macrophages are deficient in SP-R210L expressing only SP-R210S. Accordingly, SR-A-/- mice were highly susceptible to both Eap+ and Eap- S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210L mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A.
UR - https://www.scopus.com/pages/publications/79953014130
UR - https://www.scopus.com/pages/publications/79953014130#tab=citedBy
U2 - 10.1074/jbc.M110.125567
DO - 10.1074/jbc.M110.125567
M3 - Article
C2 - 21123169
AN - SCOPUS:79953014130
SN - 0021-9258
VL - 286
SP - 4854
EP - 4870
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -