Pro-inflammatory cytokine responses to Naegleria fowleri infection

Abstract

Naegleria fowleri, or the "brain-eating amoeba," is responsible for a rare, but lethal, infection known as primary amoebic meningoencephalitis (PAM). Confirmed PAM cases have seen both a rise in numbers, as well as expansion of geographic range over the past several decades. There is no effective therapy for PAM and the clinical prognosis remains grim with a mortality rate over 95%. The role of the immune response in disease prevention and disease severity remains unclear. In this review, we explore potential roles of inflammatory immune responses to N. fowleri in disease pathogenesis with a primary focus on pro-inflammatory cytokines IL-1, IL-6, and TNFα. We also discuss modulating proinflammatory cytokines as an additional immune therapy in PAM treatment.

Keywords: CNS infection; Naegleria fowleri; eukaryotic pathogen; immune response to Naegleria; immunopathology; neuroinvasion; olfactory infection; primary amoebic meningoencephalitis.

FIGURE 1

In vitro studies suggest a model for pro-inflammatory cytokine production during N. fowleri infection. N. fowleri attach to the olfactory epithelium and invade into the olfactory bulb through OSN axon tract. In the olfactory epithelium layer, resident macrophages and sustentacular cells may secrete pro-inflammatory cytokines in response to N. fowleri. In the olfactory bulb, microglia, astrocytes, endothelial cells, and macrophages may produce multiple pro- inflammatory cytokines after N. fowleri exposure. These cytokines likely play important anti- amoebic roles, but are also immunopathologic.