Transcriptomic profile of Anopheles gambiae Kisumu mosquitoes infected by neglected malaria parasite Plasmodium ovale from gametocyte-carriers in Cameroon

Abstract

Successful transmission of malaria depends on the complex interactions between the Anopheles mosquito vector and the Plasmodium parasites. Plasmodium ovale, a neglected malaria parasite, successfully develops from ookinete to sporozoite within the Anopheles vector. To elucidate the molecular mechanisms underlying this interaction, we compared RNA-seq-based gene expression profiles of Anopheles gambiae infected with P. ovale and uninfected mosquitoes at 24 hours, 9 days, and 17 days post-infection. The results showed that 2,885 P. ovale transcripts were present only 24 hours after infection. During ookinete invasion (24 h post-infection), differential gene expression analyses revealed the up-regulation of genes related to metabolic processes and the down-regulation of genes associated with cytoskeletal activity in the mosquito. Notably, the non-immune genes with unspecific function AGAP003776, (Fold Change, FC 132.0), AGAP003777, (FC 88.3), and AGAP003778, (FC 104.1), Troponin C (Fold Change, FC 85) and Myofilin (FC 33.3) exhibited the most significant overexpression. Among the immune genes that were upregulated CTL3 (FC 55.9), CLIPB12 (FC 49.4), CTLMA5 (FC 14.5), TRYP7 (FC 24.4), CLIP C9 (FC 12.1) TRYP5 (FC 12.2), LRIM10 (FC 11.2), PPO6 (FC 7.7). This initial analysis of the interaction between P. ovale and An. gambiae identified several well-known candidates for transmission-blocking strategies, including LRIM1, APN1, and D7 family proteins. In addition, new potential candidates, including AGAP003776, AGAP003777, and AGAP003778 cluster, CLIPB12, LRIM10, the APN cluster, AGAP004860, ABCC9, CYP9K1 and GSTD3 were identified. These potential new candidate genes could play a significant role in the development of transmission-blocking strategies for An. gambiae infected with Plasmodium, particularly P. ovale. The urgent functional validation of these genes is required.