Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe complement anaphylatoxin C5a contributes to host defense against Staphylococcus aureus. In this study, we investigated the functional role of the two known C5a receptors, C5aR1 and C5aR2, in the host response to S. aureus. We found that C5aR1(-/)(-) mice exhibited greater susceptibility to S. aureus bloodstream infection than wild type and C5aR2(-/)(-) mice, as demonstrated by the significantly higher bacterial loads in the kidneys and heart at 24 h of infection, and by the higher levels of inflammatory IL-6 in serum. Histological and immunohistochemistry investigation of infected kidneys at 24 h after bacterial inoculation revealed a discrete infiltration of neutrophils in wild type mice but already well-developed abscesses consisting of bacterial clusters surrounded by a large number of neutrophils in both C5aR1(-/)(-) and C5aR2(-/)(-) mice. Furthermore, blood neutrophils from C5aR1(-/)(-) mice were less efficient than those from wild type or C5aR2(-/)(-) mice at killing S. aureus. The requirement of C5aR1 for efficient killing of S. aureus was also demonstrated in human blood after disrupting C5a-C5aR1 signaling using specific inhibitors. These results demonstrated a role for C5aR1 in S. aureus clearance as well as a role for both C5aR1 and C5aR2 in the orchestration of the inflammatory response during infection.
CitationDifferential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection. 2015, 4 (4):722-38 Pathogens
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
JournalPathogens (Basel, Switzerland)
The following license files are associated with this item:
- Structure and characterization of a high affinity C5a monoclonal antibody that blocks binding to C5aR1 and C5aR2 receptors.
- Authors: Colley CS, Popovic B, Sridharan S, Debreczeni JE, Hargeaves D, Fung M, An LL, Edwards B, Arnold J, England E, Eghobamien L, Sivars U, Flavell L, Renshaw J, Wickson K, Warrener P, Zha J, Bonnell J, Woods R, Wilkinson T, Dobson C, Vaughan TJ
- Issue date: 2018 Jan
- Distinct roles of the anaphylatoxin receptors C3aR, C5aR1 and C5aR2 in experimental meningococcal infections.
- Authors: Muenstermann M, Strobel L, Klos A, Wetsel RA, Woodruff TM, Köhl J, Johswich KO
- Issue date: 2019 Dec
- Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair.
- Authors: Kovtun A, Bergdolt S, Hägele Y, Matthes R, Lambris JD, Huber-Lang M, Ignatius A
- Issue date: 2017 Oct 25
- Role of complement anaphylatoxin receptors in a mouse model of acute burn-induced pain.
- Authors: Morgan M, Deuis JR, Woodruff TM, Lewis RJ, Vetter I
- Issue date: 2018 Feb
- C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma.
- Authors: Nabizadeh JA, Manthey HD, Panagides N, Steyn FJ, Lee JD, Li XX, Akhir FNM, Chen W, Boyle GM, Taylor SM, Woodruff TM, Rolfe BE
- Issue date: 2019 Jul 12