| dc.description.abstract | The immune and circulatory systems are functionally integrated in the African malaria mosquito, Anopheles gambiae. This functional integration is exemplified by a subpopulation of hemocytes called periostial hemocytes that resides around the heart valves, which are the areas of the body that experience the highest hemolymph flow. Periostial hemocytes phagocytose bacteria and malaria parasites, and infection induces the further aggregation of hemocytes on the heart, amplifying this heart-associated immune response. At the onset of this dissertation, we had gained an understanding of the structural mechanics of this process, but the genetic mechanisms that drive periostial hemocyte aggregation remained largely unknown. This dissertation utilized a combination of RNA sequencing, RNA interference, infections and organismal manipulations to determine that (i) Thioester-containing proteins – a family of pattern recognition receptors – positively regulate periostial hemocyte aggregation, (ii) the IMD and JNK pathways – two immune signaling pathways – positively drive periostial hemocyte aggregation, and (iii) transglutaminase 3 negatively regulates periostial hemocyte aggregation, presumably by inhibiting the IMD pathway. Moreover, at the onset of this work the infection-induced aggregation of periostial hemocytes had only been described in A. gambiae. Therefore, this dissertation also explored whether periostial hemocyte aggregation is conserved in class Insecta. Analysis of 68 insect species from 51 families across 16 orders revealed that an infection induces the aggregation of hemocytes and pathogens on the heart of insects from all major branches of the class Insecta. Therefore, in a manner functionally analogous to how the spleen and lymph nodes of vertebrate animals capture pathogens circulating in the blood and lymph, the functional integration of the immune and circulatory systems is conserved throughout insect evolution. Altogether, this dissertation uncovered the genetic mechanisms and evolutionary conservation of the functional integration between the insect immune and circulatory systems. | |
