A Receptor Guanylate Cyclase, Gyc76C, Mediates Humoral, and Cellular Responses in Distinct Ways in Drosophila Immunity
Year: 2020
Type: article
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.
Source: Frontiers in Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Ministry of Education, Culture, Sports, Science and Technology, Astellas Pharma, Astellas Foundation for Research on Metabolic Disorders, National Institutes of Health, Biotechnology and Biological Sciences Research Council, Japan Society for the Promotion of Science, Japan Science and Technology Agency, National Institute of Allergy and Infectious Diseases, Institute of Genetics
Awards: G1440551734, Regulation of humoral and cellular immune responses by innate immune receptor Gyc76C in Drosophila, G2835404642, G3076600716, Molecular and Cellular Mechanisms of Host Defense, Analysis of novel cGMP pathway regulating innate immune responses, Genome analysis for innate immune memory, G4471732494, Cyclic nucleotide signalling in innate immunity, 新しい機能獲得変異体スクリーニングによる自然免疫の分子機構の解明, G6076470985, Studies of modulation mechanisms of NF-kB signaling by novel cGMP pathway, Drosophila Toll signaling regulated by novel E3 ligase Sherpa, G8514314733, G8561213674, Japan-Systems Approaches to Addressing Food Security: Novel methodology for pest control using key regulators of insect survival against infection
OpenAlex ID: W3004315662