Acute Plasmodium Infection Promotes Interferon-Gamma Dependent Resistance to Ebola Virus Infection

Abstract

During the 2013-2016 Ebola virus epidemic, a significant number of patients admitted to Ebola Treatment Units were co-infected with Plasmodium falciparum, a predominant agent of malaria. However, there is no consensus on how malaria impacts EBOV infection. The effect of acute Plasmodium infection on EBOV challenge was investigated using mouse adapted Ebola virus and a BSL-2 model virus. We demonstrate that acute Plasmodium infection protects from lethal viral challenge, dependent upon interferon gamma (IFN-γ) elicited as a result of parasite infection. Plasmodium-infected mice lacking the IFN-γ receptor were not protected. Ex vivo incubation of naïve human or mouse macrophages with sera from acutely parasitemic animals programmed a proinflammatory phenotype dependent on IFN-γ and rendered cells resistant to EBOV infection. We conclude that acute Plasmodium infection can safeguard against EBOV by production of protective IFN-γ. These findings have implications for anti-malaria therapies administered during episodic EBOV outbreaks in Africa.

Keywords: Plasmodium, Ebola virus, Macrophage polarization, Co-infection, Interferon gamma, malaria, Filovirus:Pro-inflammatory