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.
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, WT mice 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-R210(L) and SP-R210(S). The results show that WT alveolar macrophages are distinguished by expression of SP-R210(L), whereas SR-A(-/-) alveolar macrophages are deficient in SP-R210(L) expressing only SP-R210(S). 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-R210(L) 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.
Center of Biomedical Research, University of Texas Health Science Center, Tyler, Texas 75708-3154, USA. chroneos@uthct.edu
Zvjezdana
Z
Sever-Chroneos
Agnieszka
A
Krupa
Jeremy
J
Davis
Misbah
M
Hasan
Ching-Hui
CH
Yang
Jacek
J
Szeliga
Mathias
M
Herrmann
Muzafar
M
Hussain
Brian V
BV
Geisbrecht
Lester
L
Kobzik
Zissis C
ZC
Chroneos
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D008168:Lung / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000502:physiology; D011023:Pneumonia, Staphylococcal / Q000235:genetics / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
D018829:Adhesins, Bacterial; D037662:Pulmonary Surfactant-Associated Protein A; D011956:Receptors, Cell Surface; C067774:surfactant protein A receptor