Host-Malaria Parasite Interactions and Impacts on Mutual Evolution

Abstract

Malaria is the most deadly parasitic disease, affecting hundreds of millions of people worldwide. Malaria parasites have been associated with their hosts for millions of years. During the long history of host-parasite co-evolution, both parasites and hosts have applied pressure on each other through complex host-parasite molecular interactions. Whereas the hosts activate various immune mechanisms to remove parasites during an infection, the parasites attempt to evade host immunity by diversifying their genome and switching expression of targets of the host immune system. Human intervention to control the disease such as antimalarial drugs and vaccination can greatly alter parasite population dynamics and evolution, particularly the massive applications of antimalarial drugs in recent human history. Vaccination is likely the best method to prevent the disease; however, a partially protective vaccine may have unwanted consequences that require further investigation. Studies of host-parasite interactions and co-evolution will provide important information for designing safe and effective vaccines and for preventing drug resistance. In this essay, we will discuss some interesting molecules involved in host-parasite interactions, including important parasite antigens. We also discuss subjects relevant to drug and vaccine development and some approaches for studying host-parasite interactions.

Zoonotic Transmission and Host Switches of Malaria Parasites

“…Indeed, P. falciparum is closely associated with P. praefalciparum, with an estimated divergence time of 40,000-60,000 years, and signals have indicated significant gene flow between these two parasite species after their initial divergence [35]. The jump of parasites from African apes to humans was probably due to adaption and mutations in a limited number of parasite genes involved in the invasion of RBCs and host-parasite interactions [35,37]. Parasites infecting different primate hosts appear to have various genes that are involved in either invasion or pathogenesis and have been fixed in the genomes [35].…”

Primate malarias as a model for cross-species parasite transmission

“…Parasites have complementary proteins that bind receptors on the surface of host red blood cells in order to enter host cells. Notably, Duffy binding proteins (DBPs) and reticulocyte binding proteins (RBPs) (Adams & Mueller 2017;Lim et al 2017;Su et al 2020;VanBuskirk et al 2004;Carlton at al. 2008).…”

“…Understanding the strain-specific immune responses and range of natural genetic variation is particularly important because var genes such as PfEMP1 have been proposed as vaccine targets, and expression of var genes has been shown to change in response to treatments (Bachmann et al 2019;Jensen et al 2020). Su et al (2020) further discuss the role of these gene families in hostparasite interaction, and further work expanding to non-human malarias will be important to understand the role of these genes in between-species susceptibility and host switching.…”

“…Genes identified in host and parasites as important for host specificity and switching will also be potential pathways to target therapies and vaccines-both to prevent new malaria emergence in humans, and as an independent line of evidence of gene functional significance in disease. For example, DBPs are one of the proposed vaccine targets for P. vivax-related malarias because they induce protective immune responses in primate hosts (Costa et al 2015;Chitnis & Sharma 2008;Mueller et al 2015;Chen et al 2016;Su et al 2020). Host and parasite variants in the associate proteins that interact on red blood cells determines the immunity induced; therefore, an understanding of natural variation across primates will inform future vaccine design (Chen et al 2016;Su et al 2020).…”

“…For example, DBPs are one of the proposed vaccine targets for P. vivax-related malarias because they induce protective immune responses in primate hosts (Costa et al 2015;Chitnis & Sharma 2008;Mueller et al 2015;Chen et al 2016;Su et al 2020). Host and parasite variants in the associate proteins that interact on red blood cells determines the immunity induced; therefore, an understanding of natural variation across primates will inform future vaccine design (Chen et al 2016;Su et al 2020). Indeed, the high levels of genetic variation in P. vivax have been proposed as a barrier to an effective vaccine (Lim et al 2017).…”