Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues

Abstract

The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit fly Drosophila melanogaster employs multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi. Drosophila has been shown to be a powerful in vivo model for studying the mechanism of innate immunity and host-pathogen interactions because Drosophila and higher organisms share conserved signaling pathways and factors. Moreover, the ease with which Drosophila genetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated in Drosophila innate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration in Drosophila will help us better study human innate immunity-related diseases.

Chronic exposure to the star polycation (SPc) nanocarrier in the larval stage adversely impairs life history traits in Drosophila melanogaster

“…The induction of Drs was further visualized by a GFP reporter gene, which is expressed under the control of the Drs promoter and is able to faithfully reproduce the transcription pattern of the endogenous Drs gene [ 33 ]. SPc nanoparticles induced Drs-GFP in fly larval fat body cells but not in salivary gland nor intestine cells, which is consistent with the crucial role of fat body to produce antimicrobial peptides in systemic immune response [ 57 ].…”

The Intestinal Immune Defense System in Insects

“…In conjugation with the Duox and Imd signaling pathways which are two major complementary immune defense pathways in the insect gut, there are other pathways that activate AMPs to participate in the immune defense response, such as the activation of the midgut JAK/STAT pathway that induces Drosomycin expression to defend against fungal invasion [ 138 , 139 , 140 , 141 ]. The pathway is conserved throughout biological evolution and plays an important role in insect innate immunity [ 141 , 142 ].…”

Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling

“…The link between neurodegeneration and innate immunity has been the subject of much research in recent years [1][2][3][4] . Innate immunity consists of two main branches: the cellular branch, or phagocytosis, and the humoral branch, which is comprised of signaling pathways culminating in the release of cytokines, antimicrobial peptides (AMPs), and other immune molecules 5,6 . One aspect of innate immunity, inflammation, can be defined as the activation of immune cells coupled with the release of inflammatory cytokines.…”

“…The humoral immune response in Drosophila is mediated primarily by two NFkB signaling pathways, Toll and Immune deficiency (Imd) 5,6,17 . These pathways activate transcription of antimicrobial peptides (AMPs) primarily in the fat body, a tissue with similarities to the vertebrate liver.…”

“…However, there are additional complexities to these immune pathways. While AMPs are known to target bacteria and fungi, they have also been shown to contribute to neurodegeneration and other processes 5,7 . Moreover, the Toll and Imd pathways activate transcription of other genes, are expressed in multiple tissues and act in concert with other pathways and phagocytic cells to remove invading pathogens 5,17 .…”