Journal
INFECTION AND IMMUNITY
Volume 84, Issue 4, Pages 930-939Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.01520-15
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Funding
- Swedish Medical Society [SLS-496741, SLS-402871]
- Scandinavian Society for Antimicrobial Chemotherapy Foundation [SLS-501701]
- Adlerbertska Stiftelserna (Adlerbertska Foundations)
- Vetenskapsradet (VR) [D0275001, D0275002]
- Stiftelserna Wilhelm och Martina Lundgrens (Wilhelm and Martina Lundgren Foundation)
- Stiftelsen Clas Groschinskys Minnesfond (Clas Groschinski Memorial Foundation) [M1566, M14099]
- Rune och Ulla Amlovs Stiftelse for Neurologisk och Reumatologisk Forskning (Rune och Ulla Amlovs Stiftelse)
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The complement system plays an essential role in the innate immune response and protection against bacterial infections. However, detailed knowledge regarding the role of complement in Staphylococcus aureus septic arthritis is still largely missing. In this study, we elucidated the roles of selected complement proteins in S. aureus septic arthritis. Mice lacking the complement component 3 (C3(-/-)), complement factor B (fB(-/-)), and receptor for C3-derived anaphylatoxin C3a (C3aR(-/-)) and wild-type (WT) control mice were intravenously or intra-articularly inoculated with S. aureus strain Newman. The clinical course of septic arthritis, as well as histopathological and radiological changes in joints, was assessed. After intravenous inoculation, arthritis severity and frequency were significantly higher in C3(-/-) mice than in WT controls, whereas fB(-/-) mice displayed intermediate arthritis severity and frequency. This was in accordance with both histopathological and radiological findings. C3, but not fB, deficiency was associated with greater weight loss, more frequent kidney abscesses, and higher bacterial burden in kidneys. S. aureus opsonized with C3(-/-) sera displayed decreased uptake by mouse peritoneal macrophages compared with bacteria opsonized with WT or fB(-/-) sera. C3aR deficiency had no effect on the course of hematogenous S. aureus septic arthritis. We conclude that C3 deficiency increases susceptibility to hematogenous S. aureus septic arthritis and impairs host bacterial clearance, conceivably due to diminished opsonization and phagocytosis of S. aureus.
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