Mosquito cellular immunity at single-cell resolution

Abstract

Hemocytes limit the capacity of mosquitoes to transmit human pathogens. Here we profile the transcriptomes of 8506 hemocytes of Anopheles gambiae and Aedes aegypti mosquito vectors. Our data reveal the functional diversity of hemocytes, with different subtypes of granulocytes expressing distinct and evolutionarily conserved subsets of effector genes. A previously unidentified cell type in An. gambiae, which we term “megacyte,” is defined by a specific transmembrane protein marker (TM7318) and high expression of lipopolysaccharide-induced tumor necrosis factor–α transcription factor 3 (LL3). Knockdown experiments indicate that LL3 mediates hemocyte differentiation during immune priming. We identify and validate two main hemocyte lineages and find evidence of proliferating granulocyte populations. This atlas of medically relevant invertebrate immune cells at single-cell resolution identifies cellular events that underpin mosquito immunity to malaria infection.

DRscDB: A single-cell RNA-seq resource for data mining and data comparison across species

“…Next, to demonstrate the power of this feature across species, we compared Drosophila blood marker genes [6] with marker genes derived from A. gambiae (mosquito) blood scRNA-seq [17] . Of note, Drosophila blood cluster ‘PM2′ significantly correlated to ‘HC4′ in mosquito blood, both of which have been described as proliferating hemocytes that express mitotic marker genes [6] , [17] . Likewise, ‘PM6′ in flies mapped well to HC6 in mosquitoes, and both clusters are enriched in genes that encode antimicrobial peptides (AMP).…”

“…Likewise, ‘PM6′ in flies mapped well to HC6 in mosquitoes, and both clusters are enriched in genes that encode antimicrobial peptides (AMP). In addition, the ‘HC1′ cluster identified in the mosquito blood study maps to mature crystal cell cluster ‘CC2′, and both express high mRNA levels of prophenoloxidases (PPO), which are characteristics of crystal cells or otherwise called oenocytoids [6] , [17] . Interestingly, ‘HC1′ also highly correlated with ‘PM8′, a plasmatocyte cluster that is enriched in peroxiredoxins.…”

“…A. Comparison of the top 10 marker genes per cluster derived from Drosophila [6] or mosquito [17] blood scRNA-seq datasets. B.…”

Distinct Roles of Hemocytes at Different Stages of Infection by Dengue and Zika Viruses in Aedes aegypti Mosquitoes

“…For example, phagocytosis might be important to clear viruses from the circulation but, in the midgut, could help virus dissemination. However, recent single cell analyses have indicated that hemocytes are composed of many subgroups that likely have distinct functions in immunity (43)(44)(45)(46). Based on these data, it is possible that epithelial and systemic responses to viral infections mobilize different subtypes of hemocytes.…”

Mosquito Trilogy: Microbiota, Immunity and Pathogens, and Their Implications for the Control of Disease Transmission

“…They influence many aspects of the mosquito biology, including reproduction, development, adult survival and, overall, immunity (Coon et al, 2014). The main sites where cellular and humoral components of adult mosquito immunity exert their functions against invaders are the hemocoel with the circulating hemolymph, that contains the immune cells called hemocytes (Hillyer, 2010(Hillyer, , 2016Raddi et al, 2020), and the gut, which receives the sugar and blood meals and that hosts a major component of the insect microbiota (gutassociated microbiota).…”