TY - JOUR
T1 - Complement and Bacterial Infections
T2 - From Molecular Mechanisms to Therapeutic Applications
AU - Heesterbeek, Dani A.C.
AU - Angelier, Mathieu L.
AU - Harrison, Richard A.
AU - Rooijakkers, Suzan H.M.
N1 - Funding Information:
The work was funded by an ERC Starting grant (639209-Com-Bact) and the EMBO Young Investigator Program (to S.H.M.R). The authors thank Dr. Helen Leavis for critically reviewing the manuscript.
Publisher Copyright:
© 2018 S. Karger AG, Basel.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Complement is a complex protein network of plasma, and an integral part of the innate immune system. Complement activation results in the rapid clearance of bacteria by immune cells, and direct bacterial killing via large pore-forming complexes. Here we review important recent discoveries in the complement field, focusing on interactions relevant for the defense against bacteria. Understanding the molecular interplay between complement and bacteria is of great importance for future therapies for infectious and inflammatory diseases. Antibodies that support complement-dependent bacterial killing are of interest for the development of alternative therapies to treat infections with antibiotic-resistant bacteria. Furthermore, a variety of novel therapeutic complement inhibitors have been developed to prevent unwanted complement activation in autoimmune inflammatory diseases. A better understanding of how such inhibitors may increase the risk of bacterial infections is essential if such therapies are to be successful.
AB - Complement is a complex protein network of plasma, and an integral part of the innate immune system. Complement activation results in the rapid clearance of bacteria by immune cells, and direct bacterial killing via large pore-forming complexes. Here we review important recent discoveries in the complement field, focusing on interactions relevant for the defense against bacteria. Understanding the molecular interplay between complement and bacteria is of great importance for future therapies for infectious and inflammatory diseases. Antibodies that support complement-dependent bacterial killing are of interest for the development of alternative therapies to treat infections with antibiotic-resistant bacteria. Furthermore, a variety of novel therapeutic complement inhibitors have been developed to prevent unwanted complement activation in autoimmune inflammatory diseases. A better understanding of how such inhibitors may increase the risk of bacterial infections is essential if such therapies are to be successful.
KW - Antibiotic resistance
KW - Antibody therapy
KW - Bacteria
KW - Complement
KW - Eculizumab
KW - Infections
KW - Inflammatory diseases
KW - Membrane attack complex
KW - Neisseria
UR - http://www.scopus.com/inward/record.url?scp=85053028675&partnerID=8YFLogxK
U2 - 10.1159/000491439
DO - 10.1159/000491439
M3 - Review article
C2 - 30149378
AN - SCOPUS:85053028675
SN - 1662-811X
VL - 10
SP - 455
EP - 464
JO - Journal of Innate Immunity
JF - Journal of Innate Immunity
IS - 5-6
ER -