TY - JOUR
T1 - A Receptor Guanylate Cyclase, Gyc76C, Mediates Humoral, and Cellular Responses in Distinct Ways in Drosophila Immunity
AU - Iwashita, Shinzo
AU - Suzuki, Hiroaki
AU - Goto, Akira
AU - Oyama, Tomohito
AU - Kanoh, Hirotaka
AU - Kuraishi, Takayuki
AU - Fuse, Naoyuki
AU - Yano, Tamaki
AU - Oshima, Yoshiteru
AU - Dow, Julian A.T.
AU - Davies, Shireen Anne
AU - Kurata, Shoichiro
N1 - Funding Information:
We thank K. V. Anderson, D. Ferrandon, J. A. Hoffmann, D. Hultmark, J. L. Imler, Y. T. Ip, A. L. Kolodkin, B. Lemaitre, T. Muta, N. Perrimon, J. M. Reichhart, J. Royet, the Bloomington Stock Center, the Drosophila Genomics Resource Center at Indiana University, the Drosophila Genetic Resource Center at the Kyoto Institute of Technology, the Drosophila RNAi Screening Center, the Genetic Strain Research Center of the National Institute of Genetics, and the Vienna Drosophila RNAi Center for fly stocks and materials. Funding. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT 19H03365, 16H05084, 24390014, 21117005, 21117001, and 14657577); the Japan Society for the Promotion of Science (JSPS); Japan Science and Technology Agency (JST); the Program for the Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN); the Strategic International Cooperative program from the Japan Science and Technology Agency; the National Institutes of Health (AI07495); the Takeda Science Foundation; the Mitsubishi Foundation; the Astellas Foundation for Research on Metabolic Disorders; the Uehara Memorial Foundation; the Naito Foundation; a Global COE Research Grant (Tohoku University Ecosystem Adaptability); and the Biotechnological and Biological Research Sciences Council (UK) grant number BB/E011438/1 to S-AD and JD.
Funding Information:
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT 19H03365, 16H05084, 24390014, 21117005, 21117001, and 14657577); the Japan Society for the Promotion of Science (JSPS); Japan Science and Technology Agency (JST); the Program for the Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN); the Strategic International Cooperative program from the Japan Science and Technology Agency; the National Institutes of Health (AI07495); the Takeda Science Foundation; the Mitsubishi Foundation; the Astellas Foundation for Research on Metabolic Disorders; the Uehara Memorial Foundation; the Naito Foundation; a Global COE Research Grant (Tohoku University Ecosystem Adaptability); and the Biotechnological and Biological Research Sciences Council (UK) grant number BB/E011438/1 to S-AD and JD.
Publisher Copyright:
© Copyright © 2020 Iwashita, Suzuki, Goto, Oyama, Kanoh, Kuraishi, Fuse, Yano, Oshima, Dow, Davies and Kurata.
PY - 2020/1/28
Y1 - 2020/1/28
N2 - 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.
AB - 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.
KW - Drosophila
KW - cellular immune responses
KW - humoral immune responses
KW - innate immunity
KW - receptor-type guanylate cyclase
UR - http://www.scopus.com/inward/record.url?scp=85079496058&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079496058&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.00035
DO - 10.3389/fimmu.2020.00035
M3 - Article
C2 - 32063902
AN - SCOPUS:85079496058
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 35
ER -