Correlates of severity of disease in Macaca mulatta infected with Plasmodium cynomolgi

Characterization of host responses associated with severe malaria through an integrative approach is necessary to understand how Plasmodium cynolmogi infection is controlled. In this study, we conducted temporal immune profiling, cytokine profiling and transcriptomic analysis of five Macaca mulatta infected with P. cynomolgi. This experiment resulted in one death, two severe infections, and two mild infections. Our analysis reveals that differential transcriptional up-regulation of genes linked with response to pathogen-associated molecular pattern (PAMP) and pro-inflammatory cytokines is characteristic of hosts experiencing severe malaria. Furthermore, our analysis discovered associations of transcriptional differential regulation unique to severe hosts with specific cellular and cytokine responses. The combined data provide a molecular and cellular basis for the development of severe malaria during P. cynolmogi infection.