Alternative pathway regulation by factor H modulates Streptococcus pneumoniae induced proinflammatory cytokine responses by decreasing C5a receptor crosstalk
Publication year
2016Source
Cytokine, 88, (2016), pp. 281-286ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Laboratory Medicine
Paediatrics - OUD tm 2017
Biomolecular Chemistry
Journal title
Cytokine
Volume
vol. 88
Page start
p. 281
Page end
p. 286
Subject
Bio-Molecular Chemistry; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life SciencesAbstract
Bacterial pathogens not only stimulate innate immune receptors, but also activate the complement system. Crosstalk between complement C5a receptor (C5aR) and other innate immune receptors is known to enhance the proinflammatory cytokine response. An important determinant of the magnitude of complement activation is the activity of the alternative pathway, which serves as an amplification mechanism for complement activation. Both alternative pathway activity as well as plasma levels of factor H, a key inhibitor of the alternative pathway, show large variation within the human population. Here, we studied the effect of factor H-mediated regulation of the alternative pathway on bacterial-induced proinflammatory cytokine responses. We used the human pathogen Streptococcus pneumoniae as a model stimulus to induce proinflammatory cytokine responses in human peripheral blood mononuclear cells. Serum containing active complement enhanced pneumococcal induced proinflammatory cytokine production through C5a release and C5aR crosstalk. We found that inhibition of the alternative pathway by factor H, with a concentration equivalent to a high physiological level, strongly reduced C5a levels and decreased proinflammatory cytokine production in human peripheral blood mononuclear cells. This suggests that variation in alternative pathway activity due to variation in factor H plasma levels affects individual cytokine responses during infection.
This item appears in the following Collection(s)
- Academic publications [227613]
- Electronic publications [107273]
- Faculty of Medical Sciences [86193]
- Faculty of Science [33762]
- Open Access publications [76399]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.