TY - JOUR
T1 - Complement factor H serum levels determine resistance to pneumococcal invasive disease
AU - Van Der Maten, Erika
AU - Westra, Dineke
AU - Van Selm, Saskia
AU - Langereis, Jeroen D.
AU - Bootsma, Hester J.
AU - Van Opzeeland, Fred J.H.
AU - De Groot, Ronald
AU - Ruseva, Marieta M.
AU - Pickering, Matthew C.
AU - Van Den Heuvel, Lambert P.W.J.
AU - Van De Kar, Nicole C.A.J.
AU - De Jonge, Marien I.
AU - Van Der Flier, Michiel
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Streptococcus pneumoniae is a major cause of life-threatening infections. Complement activation plays a vital role in opsonophagocytic killing of pneumococci in blood. Initial complement activation via the classical and lectin pathways is amplified through the alternative pathway amplification loop. Alternative pathway activity is inhibited by complement factor H (FH). Our study demonstrates the functional consequences of the variability in human serum FH levels on host defense. Using an in vivo mouse model combined with human in vitro assays, we show that the level of serum FH correlates with the efficacy of opsonophagocytic killing of pneumococci. In summary, we found that FH levels determine a delicate balance of alternative pathway activity, thus affecting the resistance to invasive pneumococcal disease. Our results suggest that variation in FH expression levels, naturally occurring in the human population, plays a thus far unrecognized role in the resistance to invasive pneumococcal disease.
AB - Streptococcus pneumoniae is a major cause of life-threatening infections. Complement activation plays a vital role in opsonophagocytic killing of pneumococci in blood. Initial complement activation via the classical and lectin pathways is amplified through the alternative pathway amplification loop. Alternative pathway activity is inhibited by complement factor H (FH). Our study demonstrates the functional consequences of the variability in human serum FH levels on host defense. Using an in vivo mouse model combined with human in vitro assays, we show that the level of serum FH correlates with the efficacy of opsonophagocytic killing of pneumococci. In summary, we found that FH levels determine a delicate balance of alternative pathway activity, thus affecting the resistance to invasive pneumococcal disease. Our results suggest that variation in FH expression levels, naturally occurring in the human population, plays a thus far unrecognized role in the resistance to invasive pneumococcal disease.
KW - Alternative pathway
KW - C3 opsonization
KW - Complement system
KW - Factor H
KW - Invasive pneumococcal disease
KW - Streptococcus pneumoniae
UR - https://www.scopus.com/pages/publications/84978698087
U2 - 10.1093/infdis/jiw029
DO - 10.1093/infdis/jiw029
M3 - Article
C2 - 26802141
AN - SCOPUS:84978698087
SN - 0022-1899
VL - 213
SP - 1820
EP - 1827
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -