Research at the IHM uncovers pleiotropic effects of the anaphylatoxin receptors on experimental meningococcal sepsis07/31/2019
In the study of Muenstermann et al. published in Virulence (https://www.tandfonline.com/doi/full/10.1080/21505594.2019.1640035) distinct roles of the individual receptors for the complement split fragments C3a and C5a were identified during experimental sepsis in mice caused by Neisseria meningitidis. The complement system is the most important immune determinant against invasive meningococcal disease by lysis of the bacteria through the membrane attack complex. However, complement activation also releases the complement split fragments (‘anaphylatoxins’) C3a and C5a, which trigger a set of receptors, C3aR, C5aR1 and C5aR2, expressed on a multitude of immune and non-immune cell types. While C5aR1 engagement is known to trigger cellular inflammation responses, the roles of C3aR and C5aR1 are less well characterized. The results of this study show that C3aR, which responds to C3a, has a functionally distinct role than C5aR1 and C5aR2 in the mouse model of meningococcal sepsis. It became evident that interference with the C5a-C5aR1 and C5a-C5aR2 axes ameliorates disease parameters, suggesting a potential significance of both C5a-binding receptors as future drug targets. On the contrary, interference with the C3a-C3aR axis did not yield a beneficial outcome of experimental disease.