Table 2:

Major findings from vertebrate and invertebrate hosts and relevant references

Vertebrate Hosts
Major findings		References
Immune response	• Disruption of oxidative stress response by Plasmodium infection identified by transcriptomics in humans and birds, and proteomics in nonhuman primates. • T-cell activation during Plasmodium infection at transcriptome level in birds and mice. • Metabolomics data from rodents suggests immune response to Plasmodium infection affects cellular metabolic processes.	[10–15]
Malaria severity	• Transcriptome profiles of Plasmodium experienced or naïve individuals suggests interferon and cytokine mediated immune response differs depending on previous malaria exposure. • Differences in host expression seen at the transcriptome level between cerebral and uncomplicated malaria, but not in Plasmodium gene expression. • Differences in Plasmodium surface antigen expression between cerebral and uncomplicated malaria.	[19, 20, 22, 25–27, 31]
Vertebrate life cycle stages and host specificity	• Stage-specific gene expression identified in in vitro and ex vivo Plasmodium parasites. • Immune evasion proteins expressed at all Plasmodium life cycle stages. • Significant differences between avian Plasmodium and the human Plasmodium species P. vivax and P. falciparum erythrocyte invasion pathways.	[13, 14, 42–45, 56–58, 60, 62].
Invertebrate Hosts
Major findings		References
Insect-Plasmodium evolutionary arms race	• Insect oxidative stress response disrupted by oocyst development. • Significantly different insect immune response to Plasmodium compared to bacterial or viral infection found at the transcriptome and metabolome level. • Transcriptome evidence of an immune response to Plasmodium after blood meal, even when Plasmodium parasites are not present. • Significantly different immune response in phagosome activity, melanization, and complement activation during infection with drug resistant compared to non-drug resistant Plasmodium.	[66, 67, 69, 70]
Transmission between insect and vertebrate hosts	• Similar expression between P. vivax and P. falciparum in proteins involved in salivary gland and hepatocyte invasion. • Ookinete interacting proteins found in lipid rafts in insect midgut cells. • Differences in red blood cell and skin bacteria metabolomes identified in Plasmodium infected vertebrates, correlating to increased insect attraction.	[63, 87–89, 91, 92]