Characterization of cathepsin B cysteine protease from Naegleria fowleri excretory-secretory proteins exerting immunomodulatory effects

Abstract

Naegleria fowleri, a free-living amoeba that is found in diverse environmental

habitats, can cause an acute fulminating hemorrhagic meningoencephalitis, called

primary amoebic meningoencephalitis (PAM) in experimental animals and in

humans. Pathogenicity of N. fowleri may be induced by contact-dependent and

contact-independent mechanisms, and both mechanisms lead to death of host cells.

Several proteins secreted from N. fowleri are likely to be associated with contactindependent

pathogenic mechanism of the amoeba. The excretory and secretory

proteins of N. fowleri (Nf-ESPs) include phospholipase, proteases, peroxiredoxins

and thrombin receptor. However, the precise mechanism induced by Nf-ESPs in

PAM is not fully understood yet. In this study, the cytopathic changes and

inflammatory responses induced by Nf-ESPs were analyzed in BV2 microglial

cells. Several cytokines, particularly IL-1α and TNF- α were highly up-regulated

by Nf-ESPs. Also, activation of P38 and JNK was observed in BV2 cells treated

with Nf-ESPs. The results collectively suggest that Nf-ESPs may play an

important role in N. fowleri mediated-PAM through induction of inflammatory

response in microglial cells and activation of MAPKs signal pathway.