Deficiency of the complement component 3 but not factor B aggravates Staphylococcus aureus septic arthritis in mice.

• 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 (S. aureus) septic arthritis is still largely missing. In this study, we elucidated the role of selected complement proteins in S. aureus septic arthritis. Mice lacking the complement component 3 (C3(-/-)), complement factor B (fB(-/-)), receptor for C3 derived anaphylatoxin C3a (C3aR(-/-)) and wild-type (WT) control mice were intravenously or intraarticularly inoculated with Staphylococcus aureus Newman strain. The clinical course of septic arthritis as well as histopathological and radiological changes in joints were assessed. After intravenous inoculation, arthritis severity and frequency was significantly higher in C3(-/-) mice compared to 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 larger weight loss, more frequent kidney abscesses, as well as higher bacterial burden in kidneys. S. aureus opsonised with C3(-/-) sera displayed decreased uptake by mouse peritoneal macrophages compared with bacteria opsonised 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 the susceptibility to hematogenous S. aureus septic arthritis and impairs host bacterial clearance, conceivably due to diminished opsonisation and phagocytosis of S. aureus.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

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