Abstract
Innate immunity is an evolutionarily conserved host defense system against infections. The fruit fly Drosophila relies solely on innate immunity for infection defense, and the conservation of innate immunity makes Drosophila an ideal model for understanding the principles of innate immunity, which comprises both humoral and cellular responses. The mechanisms underlying the coordination of humoral and cellular responses, however, has remained unclear. Previously, we identified Gyc76C, a receptor-type guanylate cyclase that produces cyclic guanosine monophosphate (cGMP), as an immune receptor in Drosophila. Gyc76C mediates the induction of antimicrobial peptides for humoral responses by a novel cGMP pathway including a membrane-localized cGMP-dependent protein kinase, DG2, through downstream components of the Toll receptor such as dMyD88. Here we show that Gyc76C is also required for the proliferation of blood cells (hemocytes) for cellular responses to bacterial infections. In contrast to Gyc76C-dependent antimicrobial peptide induction, Gyc76C-dependent hemocyte proliferation is meditated by a small GTPase, Ras85D, and not by DG2 or dMyD88, indicating that Gyc76C mediates the cellular and humoral immune responses in distinct ways.
Highlights
The innate immune system is a powerful and evolutionarily well-conserved barrier to infectious pathogens (1, 2)
We previously identified Gyc76C as an immune receptor that is crucial for host survival against Gram-positive bacterial infections in Drosophila (Kanoh et al, under revision)
Gyc76C is preferentially expressed in immune-related tissues such as the fat body, a major organ producing antimicrobial peptides (AMPs), hemocytes involved in cellular responses, and Malphigian tubules (Kanoh et al, under revision)
Summary
The innate immune system is a powerful and evolutionarily well-conserved barrier to infectious pathogens (1, 2). The fruit fly Drosophila melanogaster is an excellent model organism for deciphering the basic principles of innate immunity, which comprises both humoral and cellular responses (3–5). Induction of antimicrobial peptides (AMPs) in the fat body, the functional equivalent of the mammalian liver, is a humoral response in Drosophila controlled by two distinct innate immune signaling pathways, the Toll and immune deficiency (imd) pathways (4, 6). The Toll and imd pathways are mechanistically similar to the mammalian nuclear factor-kappa B signaling pathways, the Toll-like receptor/interleukin-1 receptor signaling pathway and the tumor necrosis factor-α receptor signaling pathway, respectively (2). Both pathways are mediated by several factors, including the Toll receptor and Drosophila myeloid differentiation primary response 88
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