Complement Factor H Serum Levels Determine Resistance to Pneumococcal Invasive Disease.

The Journal of Infectious Diseases
Erika van der MatenMichiel van der Flier

Abstract

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.

References

Sep 1, 1996·Clinical and Experimental Immunology·C A FijenJ Dankert
Apr 12, 2001·The New England Journal of Medicine·M J Walport
Dec 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jeremy S BrownMarina Botto
May 1, 2004·Immunogenetics·Jorge Esparza-GordilloSantiago Rodríguez de Córdoba
May 28, 2004·Molecular Immunology·Santiago Rodríguez de CórdobaPilar Sánchez-Corral
Aug 30, 2006·Scandinavian Journal of Infectious Diseases·Elene HaralambousMichael Levin
Oct 6, 2006·FEMS Microbiology Letters·Lisa R QuinLarry S McDaniel
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sven HammerschmidtPeter F Zipfel
Jun 26, 2007·Cellular Microbiology·Menno van Lookeren CampagneEric J Brown
Dec 18, 2007·Clinical and Experimental Immunology·S Rodríguez de Córdoba, E Goicoechea de Jorge
Dec 18, 2007·Clinical and Experimental Immunology·C Q SchmidtP N Barlow
Jan 17, 2008·Nature Reviews. Microbiology·John D LambrisBrian V Geisbrecht
Apr 19, 2008·Journal of Cellular and Molecular Medicine·Morten Harboe, Tom Eirik Mollnes
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ling LuJing-Ren Zhang
Sep 15, 2009·Lancet·Katherine L O'BrienUNKNOWN Hib and Pneumococcal Global Burden of Disease Study Team
Oct 12, 2010·Clinical Microbiology Reviews·Sanjay RamPeter A Rice
May 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Meike HeurichClaire L Harris
Aug 10, 2011·Archives of Ophthalmology·R Theodore SmithRando Allikmets
Oct 25, 2011·PloS One·Catherine HyamsJeremy S Brown
Dec 6, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karita HaapasaloT Sakari Jokiranta
Jul 4, 2012·Trends in Immunology·Claire L HarrisB Paul Morgan
Sep 7, 2013·The Journal of Infectious Diseases·Sarah BrowallBirgitta Henriques-Normark
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Youssif Mohammed AliWilhelm J Schwaeble
Apr 1, 2015·Molecular Immunology·R B PouwD Wouters
May 21, 2015·Proceedings of the National Academy of Sciences of the United States of America·Christopher B ToomeyCatherine Bowes Rickman
Jul 23, 2015·PLoS Pathogens·David ErmertAnna M Blom

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Citations

Oct 11, 2016·Journal of Internal Medicine·Diana KarpmanIda Arvidsson
Nov 15, 2018·International Journal of Molecular Sciences·Belinda YauLay Khoon Too
May 7, 2019·The Journal of Infectious Diseases·Youssif M AliMona I Shaaban
Dec 23, 2017·Frontiers in Immunology·Zhi-Xue ChengBo Peng
Dec 31, 2019·Journal of Neuroinflammation·E Soemirien KasanmoentalibDiederik van de Beek

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