Gene expression of macaques infected with malaria species of zoonotic concern

A multitude of malaria species (genus Plasmodium) infects primates. Due to their public health importance, the human-infective species have garnered the most focus, but increased knowledge of non-human primate malaria species is warranted to improve our evolutionary understanding of host-parasite interactions. Additionally, the broad host tropism of some primate malaria parasites and their realized or theorized zoonotic potential add urgency to understanding of primate-parasite interactions. Here, we use comparative transcriptomics to understand the rhesus macaque (Macaca mulatta) response to two malaria parasites used as analogues to human-infective species of differing severity and which may represent emerging zoonotic threats: P. coatneyi, comparable to human-infective P. falciparum, and P. cynomolgi, comparable to human-infective P. vivax. We first validate our transcriptomics-based proxy of parasite load through comparison to gold-standard microscopy-based measures. We then find that malaria-associated host genes have functional links to immune system regulation and blood cells. Host genes with differing expression by malaria species were more likely to be involved in brain-linked functions, perhaps due to the differential central nervous system involvement of the two parasite species. Such comparative work on primate malaria species may help elucidate the essential and species-specific molecular mechanisms that underlie differing clinical presentations and zoonotic risk.