Interaction between Plasmodium Glycosylphosphatidylinositol and the Host Protein Moesin Has No Implication in Malaria Pathology.

Josefine Dunst,Xinyu Liu,Nahid Azzouz,Sachiko Tsukita,Peter H Seeberger,Faustin Kamena

doi:10.3389/fcimb.2017.00183

Abstract

Glycosylphosphatidylinositol (GPI) anchor of Plasmodium falciparum origin is considered an important toxin leading to severe malaria pathology through stimulation of pro-inflammatory responses from innate immune cells. Even though the GPI-induced immune response is widely described to be mediated by pattern recognition receptors such as TLR2 and TLR4, previous studies have revealed that these two receptors are dispensable for the development of severe malaria pathology. Therefore, this study aimed at the identification of potential alternative Plasmodium GPI receptors. Herein, we have identified the host protein moesin as an interaction partner of Plasmodium GPI in vitro. Given previous reports indicating the relevance of moesin especially in the LPS-mediated induction of pro-inflammatory responses, we have conducted a series of in vitro and in vivo experiments to address the physiological relevance of the moesin-Plasmodium GPI interaction in the context of malaria pathology. We report here that although moesin and Plasmodium GPI interact in vitro, moesin is not critically involved in processes leading to Plasmodium-induced pro-inflammatory immune responses or malaria-associated cerebral pathology.

Highlights

Malaria still causes a devastatingly high number of deaths and new infections each year and is thereby a major contributor to the global burden of infectious diseases (WHO, 2016)
Observations that TLR2/4 double knockout mice show no resistance to cerebral malaria (Togbe et al, 2007) prompted the question whether additional receptors might be involved in this process
Since moesin showed the highest probability after repeated experiments and given the postulated role in LPS signaling (Tohme et al, 1999; Amar et al, 2001; Iontcheva et al, 2004; Zawawi et al, 2010), moesin was selected for further investigations

Summary

Introduction

Malaria still causes a devastatingly high number of deaths and new infections each year and is thereby a major contributor to the global burden of infectious diseases (WHO, 2016). This disease is caused by human host-adapted Plasmodium species and transmitted by the bite of an infective Anopheles mosquito. Some individuals progress to a severe course of malaria, partly owing to an imbalance in the pro- and anti-inflammatory immune response (Langhorne et al, 2008), resulting in malaria-associated mortality which is largely attributed to P. falciparum infections (WHO, 2016). The precise molecular mechanisms underlying CM are not yet fully understood

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