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Alternative pathway regulation by factor H modulates Streptococcus pneumoniae induced proinflammatory cytokine responses by decreasing C5a receptor crosstalk
- Source :
- Cytokine, 88, 281-286, Cytokine, 88, pp. 281-286
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Contains fulltext : 171105.pdf (Publisher’s version ) (Open Access) 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.
- Subjects :
- Adult
Male
0301 basic medicine
Complement Pathway, Alternative
Immunology
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Complement receptor
Biology
Biochemistry
C5a receptor
Proinflammatory cytokine
03 medical and health sciences
Classical complement pathway
0302 clinical medicine
Humans
Immunology and Allergy
Receptor, Anaphylatoxin C5a
Molecular Biology
Bio-Molecular Chemistry
Hematology
Complement system
Streptococcus pneumoniae
030104 developmental biology
Complement Factor H
Factor H
Leukocytes, Mononuclear
Alternative complement pathway
Female
Interleukin 18
030215 immunology
Subjects
Details
- ISSN :
- 10434666
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Cytokine
- Accession number :
- edsair.doi.dedup.....0357fb715163727116476b852983987e
- Full Text :
- https://doi.org/10.1016/j.cyto.2016.09.025