A case-control method (488 septic patients and 527 healthy individuals) was carried out in this study to investigate the genetic relationship between CFH polymorphisms (rs3753394 C/T, rs1065489 G/T and rs1061170 C/T) and susceptibility to sepsis caused by bacterial infections in Chinese Han populations.
These novel findings suggest that FH binding to CspZ facilitates B. burgdorferi complement evasion in vivo and promotes systemic infection in vertebrate hosts.
FH6-7/Fc has previously been shown to enhance complement-dependent killing of, and facilitate bacterial clearance in, animal models of the Gram-negative pathogens <i>Haemophilus influenzae</i> and <i>Neisseria meningitidis</i> We hypothesized that activation of complement by FH6-7/Fc on the surface of Gram-positive bacteria such as <i>S. pyogenes</i> will enable professional phagocytes to eliminate the pathogen.We found that FH6-7/Fc alleviated <i>S. pyogenes-</i>induced sepsis in a transgenic mouse model expressing human FH (<i>S. pyogenes</i> binds FH in a human-specific manner).
In this study, protection against experimental sepsis caused by pneumococci carrying different PspC variants was evaluated by immunisation with the fH-binding fragment of PspC.
Homozygosity for the complement factor HY402H polymorphism, which is thought to reduce complement inhibition, was associated with less frequent SIRS/sepsis (the adjusted odds ratio for the homozygous variant complement factor HY402H [CC] carriers was 0.3, 95% confidence interval, 0.1-0.7, p = .005).
In the present study, using a mouse model of systemic infection and flow-cytometric analyses, we demonstrated an in vivo interaction between FH and pneumococci and showed differential FH binding during bacteremia.