The immune deficiency and c-Jun N-terminal kinase pathways drive the functional integration of the immune and circulatory systems of mosquitoes

Abstract

The immune and circulatory systems of animals are functionally integrated. In mammals, the spleen and lymph nodes filter and destroy microbes circulating in the blood and lymph, respectively. In insects, immune cells that surround the heart valves (ostia), called periostial haemocytes, destroy pathogens in the areas of the body that experience the swiftest haemolymph (blood) flow. An infection recruits additional periostial haemocytes, amplifying heart-associated immune responses. Although the structural mechanics of periostial haemocyte aggregation have been defined, the genetic factors that regulate this process remain less understood. Here, we conducted RNA sequencing in the African malaria mosquito, Anopheles gambiae , and discovered that an infection upregulates multiple components of the immune deficiency (IMD) and c-Jun N-terminal kinase (JNK) pathways in the heart with periostial haemocytes. This upregulation is greater in the heart with periostial haemocytes than in the circulating haemocytes or the entire abdomen. RNA interference-based knockdown then showed that the IMD and JNK pathways drive periostial haemocyte aggregation and alter phagocytosis and melanization on the heart, thereby demonstrating that these pathways regulate the functional integration between the immune and circulatory systems. Understanding how insects fight infection lays the foundation for novel strategies that could protect beneficial insects and harm detrimental ones.

Intrinsic factors driving mosquito vector competence and viral evolution: a review

“…While demonstration of dsRNA uptake by mosquito hemocytes suggests they may also play such a role, evidence of downstream RNAi activity is lacking (Airs et al, 2023). A number of sequencing experiments have also identified interconnectivity between the molecular innate immune pathways (IMD, Toll, JAK-STAT) and hemocyte activity during Plasmodium and bacterial infection of Anopheles spp, but this has not been replicated in a mosquito-virus system (Ramirez et al, 2014;Yan et al, 2022).…”

Immune Reactions of Vector Insects to Parasites and Pathogens

“…Details of mosquito phagocytic interactions with parasites and pathogens are given in other papers in this Special Issue and have been published previously [ 15 , 102 , 118 , 120 , 121 , 122 , 123 , 124 , 125 ]. Granulocytes are the main phagocytes in mosquitoes and comprise about 90% of the haemogram of which there are ca.…”

“…A fascinating study on the mosquito responses to Plasmodium has shown that infection results in recruitment of additional periosteal haemocytes to amplify the heart-related immune response. This results from the upregulation of the IMD and JNK signaling pathways (see Section 6 on recognition, below) which enhances this periosteal haemocyte aggregation, activating phagocytosis and melanisation in the heart, thereby demonstrating the integration of the response between the immune and circulatory systems [ 125 ]. The freely circulating haemocytes were not affected in a similar way.…”