Fhbp Case Studies

Introduction

Role of fHbp in the immune evasion of N. meningitidis Tom Lotze Neisseria meningitides or meningococcus is well known for causing severe diseases such as meningitis and septic shock as a result of infection, both of which are highly mortal (Seib et al. 2009). Despite these serious consequences, N. meningitidis is part of the normal flora of the nasopharynx of 40% of adults worldwide, and the infection usually goes by asymptomatically (Schneider et al. 2007; Haralambous et al. 2006). However, when the bacterium breaches the nasopharynx epithelial cells and gets into the blood this can be highly dangerous for the host.

Meningococcus has extensive mechanisms to evade the different arms of the human immune system, as reviewed by

Future research about the specific interactions between fH and fHbp can lead to a better model of N. meningitidis in the human body. This information can be used primarily in prophylactic treatment, in the form of vaccines, since the fHbp is an antigen specific for N. meningitidis (Madico et al. 2006). Already some vaccines are on the market, but they are not completely efficient and not suited for all the serotypes of N. meningitidis (Seib et al. 2009; Lo et al. 2009). One of the major challenges in developing a vaccine is the molecular mimicry of host antigens on the surface of the bacteria, possibly causing an autoimmune reaction and acting as decoy for the adaptive immune system (Lo et al.

meningitidis has extensive mechanisms to elude the host immune system, of which tactics to evade complement deposition are of major importance. The main mechanism is the recruitment of a human negative regulator of the complement system, fH, by the membrane protein fHbp. This binding, by preventing the assembly of C3 convertase, inhibits the deposition of complement on the bacterial surface and increases its chances of survival. In addition, N. meningitidis can exploit host weakness by upregulating the expression of proteins involved in immune evasion in response to elevated temperature, as is the case in fever. Future research should seek to target specific antigens on the surface and inhibitors of the fHbp-fH interaction to be able to treat or prevent this disease that can have severe