Octopamine and its Receptors are Involved in the Modulation of the Immune Response in Drosophila melanogaster

Stress is known to be a risk factor for the exacerbation of asthma and other chronic respiratory diseases. It induces the release of biogenic amines (BAs) such as norepinephrine, serotonin and dopamine, which modulate the innate and adaptive immune response. Effects of BAs on innate immunity can hardly be elucidated in complex model organisms such as the mouse due to close interactions between the innate and adaptive systems. In this light, the fruit fly Drosophila melanogaster represents a promising model system. Devoid of an adaptive immune system, the fly shares several signalling pathways with high similarities to human counterparts (e.g. Toll receptors, NF-κB signalling). It also uses analogues to human BAs (e.g. octopamine [OA], a chemical relative of norepinephrine) which activate the same signalling pathways. The flyʼs immune response comprises macrophage-like cells, called hemocytes, which phagocytise apoptotic cells and microorganisms, and the fat body, which secrets antimicrobial peptides (AMPs) to fight microbial infections. The aim of this work is to elucidate the impact of OA on the immune response of Drosophila. qRT-PCR experiments showed that two (Octβ1R, Octβ2R) out of four OA receptors are most prominently expressed in the fly. By using an infection model for Pectobacterium carotovorum, which only causes a moderate infection in wild-type flies, we were able to show that the survival rate of infected females flies deficient for the receptor Octβ1R or Octβ2R was significantly decreased compared to non-infected ones. Simultaneously, in both knockouts the bacterial load was highly increased 24 hours after bacterial injection. Moreover, qRT-PCR experiments revealed a strong upregulation of almost all antimicrobial peptide genes in infected Octβ1R-deficient female flies and even stronger in Octβ2R ones. However, the phagocytic activity of adult as well as larval Octβ1R or Octβ2R-deficient hemocytes was diminished after being challenged either in vivo or in vitro by fluorescent pHrodo E. coli bioparticles. These findings suggest that OA modulates Drosophilaʼs innate immune response and may point to a similar immune-modulatory role of norepinephrine in vertebrates.