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.

Keywords: Drosophila; immune response; innate immunity; signaling pathway; tissue communication.

Figure 1

Overview of Drosophila host defenses. (A) The hallmark of humoral immunity (also known as the systemic immune response) is antimicrobial peptides (AMPs, i.e., Diptericin, Attacin and others) secretion by the fat body; this process is mainly modulated by the Toll and Imd pathways. (B) Cellular immunity depends on three types of hemocytes in Drosophila: plasmatocytes, crystal cells and lamellocytes. In addition the lymph gland is the main hematopoietic tissue in the larval stage. Plasmatocytes and lamellocytes can phagocytose and encapsulate pathogens, respectively, and crystal cells participate in wound healing through melanization.

Figure 2

The relationship between main immune pathways, immune responses and immunological functions in Drosophila innate immunity. From top to bottom, the three rows represent the immune pathway (the Toll, Imd, JNK and JAK/STAT pathways are depicted,from left to right) (A), the immune response (B) and immunological functions (C). The red, blue, green and yellow lines indicate that the processes are related to the Toll, Imd, JNK and JAK/STAT pathways, respectively. The black lines indicate that the processes are related to other pathways. The dotted lines represent processes waiting to be confirmed. The arrows and “T” indicate promoting and inhibitory effects, respectively. The red cross indicates depletion. The scissors represent cleavage. Abbreviation: p, phosphorylation; Ub, ubiquitination; (s), short form; and (f), full length.

Figure 3

Schematic overview of tissue communication in innate immunity. In addition to autonomous regulation inside immune organs, homeostasis of the immune system is regulated by external signals emitted by other tissues, including the brain, ring glands, muscles and others. Tissue communication is largely dependent on two types of hormones: ecdysone and insulin. Moreover, ligands, including Upds, Vn and Spi, act as “messengers” in this process. Typically, the lymph gland is sensitive to nutrient status, oxygen concentration, odor signals and other environmental factors. Different processes or signaling pathways are indicated by arrows of different colors.