Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Drosophila Gut Immune Pathway Suppresses Host Development-Promoting Effects of Acetic Acid Bacteria

  • Jaegeun Lee (Department of Life Science, Chung-Ang University) ;
  • Xinge Song (Department of Life Science, Chung-Ang University) ;
  • Bom Hyun (Department of Life Science, Chung-Ang University) ;
  • Che Ok Jeon (Department of Life Science, Chung-Ang University) ;
  • Seogang Hyun (Department of Life Science, Chung-Ang University)
  • Received : 2023.08.17
  • Accepted : 2023.08.21
  • Published : 2023.10.31
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Abstract

The physiology of most organisms, including Drosophila, is heavily influenced by their interactions with certain types of commensal bacteria. Acetobacter and Lactobacillus, two of the most representative Drosophila commensal bacteria, have stimulatory effects on host larval development and growth. However, how these effects are related to host immune activity remains largely unknown. Here, we show that the Drosophila development-promoting effects of commensal bacteria are suppressed by host immune activity. Mono-association of germ-free Drosophila larvae with Acetobacter pomorum stimulated larval development, which was accelerated when host immune deficiency (IMD) pathway genes were mutated. This phenomenon was not observed in the case of mono-association with Lactobacillus plantarum. Moreover, the mutation of Toll pathway, which constitutes the other branch of the Drosophila immune pathway, did not accelerate A. pomorum-stimulated larval development. The mechanism of action of the IMD pathway-dependent effects of A. pomorum did not appear to involve previously known host mechanisms and bacterial metabolites such as gut peptidase expression, acetic acid, and thiamine, but appeared to involve larval serum proteins. These findings may shed light on the interaction between the beneficial effects of commensal bacteria and host immune activity.

Keywords

Acknowledgement

We thank Dr. Won-Jae Lee (Seoul National University) for sharing the Ap(DM001), Ap(P3G5), and Lp(WJL) bacterial strains with us. We thank the Bloomington Drosophila Stock Center for providing the fly stocks used in this study. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (grant No. 2023R1A2C1005908 and 2018R1A5A1025077). This work was supported by Chung-Ang University Research Scholarship Grants in 2022.

References

  1. Benes, H., Edmondson, R.G., Fink, P., Kejzlarovalepesant, J., Lepesant, J.A., Miles, J.P., and Spivey, D.W. (1990). Adult expression of the Drosophila Lsp-2 gene. Dev. Biol. 142, 138-146.  https://doi.org/10.1016/0012-1606(90)90157-E
  2. Bischoff, V., Vignal, C., Duvic, B., Boneca, I.G., Hoffmann, J.A., and Royet, J. (2006). Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2. PLoS Pathog. 2, e14. 
  3. Blackburn, M.B., Loeb, M.J., Clark, E., and Jaffe, H. (2004). Stimulation of midgut stem cell proliferation by Manduca sexta alpha-arylphorin. Arch. Insect Biochem. Physiol. 55, 26-32.  https://doi.org/10.1002/arch.10119
  4. Blum, J.E., Fischer, C.N., Miles, J., and Handelsman, J. (2013). Frequent replenishment sustains the beneficial microbiome of Drosophila melanogaster. mBio 4, e00860-13. 
  5. Bosco-Drayon, V., Poidevin, M., Boneca, I.G., Narbonne-Reveau, K., Royet, J., and Charroux, B. (2012). Peptidoglycan sensing by the receptor PGRPLE in the Drosophila gut induces immune responses to infectious bacteria and tolerance to microbiota. Cell Host Microbe 12, 153-165.  https://doi.org/10.1016/j.chom.2012.06.002
  6. Broderick, N.A. and Lemaitre, B. (2012). Gut-associated microbes of Drosophila melanogaster. Gut Microbes 3, 307-321.  https://doi.org/10.4161/gmic.19896
  7. Buchon, N., Broderick, N.A., Chakrabarti, S., and Lemaitre, B. (2009). Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev. 23, 2333-2344.  https://doi.org/10.1101/gad.1827009
  8. Buchon, N., Silverman, N., and Cherry, S. (2014). Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology. Nat. Rev. Immunol. 14, 796-810.  https://doi.org/10.1038/nri3763
  9. Douglas, A.E. (2018). The Drosophila model for microbiome research. Lab Anim. (N.Y.) 47, 157-164.  https://doi.org/10.1038/s41684-018-0065-0
  10. Douglas, A.E. (2019). Simple animal models for microbiome research. Nat. Rev. Microbiol. 17, 764-775.  https://doi.org/10.1038/s41579-019-0242-1
  11. Eliautout, R., Dubrana, M.P., Vincent-Monegat, C., Vallier, A., BraquartVarnier, C., Poirie, M., Saillard, C., Heddi, A., and Arricau-Bouvery, N. (2016). Immune response and survival of Circulifer haematoceps to Spiroplasma citri infection requires expression of the gene hexamerin. Dev. Comp. Immunol. 54, 7-19.  https://doi.org/10.1016/j.dci.2015.08.007
  12. Erkosar, B., Kolly, S., van der Meer, J.R., and Kawecki, T.J. (2017). Adaptation to chronic nutritional stress leads to reduced dependence on microbiota in Drosophila melanogaster. mBio 8, e01496-17. 
  13. Erkosar, B., Storelli, G., Mitchell, M., Bozonnet, L., Bozonnet, N., and Leulier, F. (2015). Pathogen virulence impedes mutualist-mediated enhancement of host juvenile growth via inhibition of protein digestion. Cell Host Microbe 18, 445-455.  https://doi.org/10.1016/j.chom.2015.09.001
  14. Fridmann-Sirkis, Y., Stern, S., Elgart, M., Galili, M., Zeisel, A., Shental, N., and Soen, Y. (2014). Delayed development induced by toxicity to the host can be inherited by a bacterial-dependent, transgenerational effect. Front. Genet. 5, 27. 
  15. Guo, L., Karpac, J., Tran, S.L., and Jasper, H. (2014). PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell 156, 109-122.  https://doi.org/10.1016/j.cell.2013.12.018
  16. Ha, E.M., Lee, K.A., Seo, Y.Y., Kim, S.H., Lim, J.H., Oh, B.H., Kim, J., and Lee, W.J. (2009). Coordination of multiple dual oxidase-regulatory pathways in responses to commensal and infectious microbes in drosophila gut. Nat. Immunol. 10, 949-957.  https://doi.org/10.1038/ni.1765
  17. Han, G., Lee, H.J., Jeong, S.E., Jeon, C.O., and Hyun, S. (2017). Comparative analysis of Drosophila melanogaster gut microbiota with respect to host strain, sex, and age. Microb. Ecol. 74, 207-216.  https://doi.org/10.1007/s00248-016-0925-3
  18. Hang, S., Purdy, A.E., Robins, W.P., Wang, Z., Mandal, M., Chang, S., Mekalanos, J.J., and Watnick, P.I. (2014). The acetate switch of an intestinal pathogen disrupts host insulin signaling and lipid metabolism. Cell Host Microbe 16, 592-604.  https://doi.org/10.1016/j.chom.2014.10.006
  19. Kamareddine, L., Robins, W.P., Berkey, C.D., Mekalanos, J.J., and Watnick, P.I. (2018). The Drosophila immune deficiency pathway modulates enteroendocrine function and host metabolism. Cell Metab. 28, 449-462. e5.  https://doi.org/10.1016/j.cmet.2018.05.026
  20. Kim, J. and Lee, H.K. (2021). The role of gut microbiota in modulating tumor growth and anticancer agent efficacy. Mol. Cells 44, 356-362. https://doi.org/10.14348/molcells.2021.0032
  21. Koranteng, F., Cho, B., and Shim, J. (2022). Intrinsic and extrinsic regulation of hematopoiesis in Drosophila. Mol. Cells 45, 101-108.  https://doi.org/10.14348/molcells.2022.2039
  22. Lee, J., Han, G., Kim, J.W., Jeon, C.O., and Hyun, S. (2020). Taxon-specific effects of Lactobacillus on Drosophila host development. Microb. Ecol. 79, 241-251.  https://doi.org/10.1007/s00248-019-01404-9
  23. Lee, J., Yun, H.M., Han, G., Lee, G.J., Jeon, C.O., and Hyun, S. (2022). A bacteria-regulated gut peptide determines host dependence on specific bacteria to support host juvenile development and survival. BMC Biol. 20, 258. 
  24. Lee, J.B., Park, K.E., Lee, S.A., Jang, S.H., Eo, H.J., Jang, H.A., Kim, C.H., Ohbayashi, T., Matsuura, Y., Kikuchi, Y., et al. (2017). Gut symbiotic bacteria stimulate insect growth and egg production by modulating hexamerin and vitellogenin gene expression. Dev. Comp. Immunol. 69, 12-22.  https://doi.org/10.1016/j.dci.2016.11.019
  25. Leulier, F., Parquet, C., Pili-Floury, S., Ryu, J.H., Caroff, M., Lee, W.J., Mengin-Lecreulx, D., and Lemaitre, B. (2003). The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nat. Immunol. 4, 478-484.  https://doi.org/10.1038/ni922
  26. Lhocine, N., Ribeiro, P.S., Buchon, N., Wepf, A., Wilson, R., Tenev, T., Lemaitre, B., Gstaiger, M., Meier, P., and Leulier, F. (2008). PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling. Cell Host Microbe 4, 147-158.  https://doi.org/10.1016/j.chom.2008.07.004
  27. Massey, H.C., Jr., KejzlarovaLepesant, J., Willis, R.L., Castleberry, A.B., and Benes, H. (1997). The Drosophila Lsp-1 beta gene a structural and phylogenetic analysis. Eur. J. Biochem. 245, 199-207.  https://doi.org/10.1111/j.1432-1033.1997.00199.x
  28. Matos, R.C. and Leulier, F. (2014). Lactobacilli-Host mutualism: "learning on the fly". Microb. Cell Fact. 13 Suppl 1, S6. 
  29. Matos, R.C., Schwarzer, M., Gervais, H., Courtin, P., Joncour, P., Gillet, B., Ma, D., Bulteau, A.L., Martino, M.E., Hughes, S., et al. (2017). D-Alanylation of teichoic acids contributes to Lactobacillus plantarum-mediated Drosophila growth during chronic undernutrition. Nat. Microbiol. 2, 1635-1647.  https://doi.org/10.1038/s41564-017-0038-x
  30. Paredes, J.C., Welchman, D.P., Poidevin, M., and Lemaitre, B. (2011). Negative regulation by amidase PGRPs shapes the Drosophila antibacterial response and protects the fly from innocuous infection. Immunity 35, 770-779.  https://doi.org/10.1016/j.immuni.2011.09.018
  31. Ryu, J.H., Kim, S.H., Lee, H.Y., Bai, J.Y., Nam, Y.D., Bae, J.W., Lee, D.G., Shin, S.C., Ha, E.M., and Lee, W.J. (2008). Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 319, 777-782.  https://doi.org/10.1126/science.1149357
  32. Sannino, D.R., Dobson, A.J., Edwards, K., Angert, E.R., and Buchon, N. (2018). The Drosophila melanogaster gut microbiota provisions thiamine to its host. mBio 9, e00155-18. 
  33. Schwarzer, M., Makki, K., Storelli, G., Machuca-Gayet, I., Srutkova, D., Hermanova, P., Martino, M.E., Balmand, S., Hudcovic, T., Heddi, A., et al. (2016). Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science 351, 854-857.  https://doi.org/10.1126/science.aad8588
  34. Shin, S.C., Kim, S.H., You, H., Kim, B., Kim, A.C., Lee, K.A., Yoon, J.H., Ryu, J.H., and Lee, W.J. (2011). Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science 334, 670-674.  https://doi.org/10.1126/science.1212782
  35. Short, C.A., Hatle, J.D., and Hahn, D.A. (2020). Protein stores regulate when reproductive displays begin in the male Caribbean fruit fly. Front. Physiol. 11, 991. 
  36. Storelli, G., Defaye, A., Erkosar, B., Hols, P., Royet, J., and Leulier, F. (2011). Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab. 14, 403-414.  https://doi.org/10.1016/j.cmet.2011.07.012
  37. Telfer, W.H. and Kunkel, J.G. (1991). The function and evolution of insect storage hexamers. Annu. Rev. Entomol. 36, 205-228.  https://doi.org/10.1146/annurev.en.36.010191.001225
  38. Tzou, P., Reichhart, J.M., and Lemaitre, B. (2002). Constitutive expression of a single antimicrobial peptide can restore wild-type resistance to infection in immunodeficient Drosophila mutants. Proc. Natl. Acad. Sci. U. S. A. 99, 2152-2157.  https://doi.org/10.1073/pnas.042411999
  39. Wong, A.C., Vanhove, A.S., and Watnick, P.I. (2016). The interplay between intestinal bacteria and host metabolism in health and disease: lessons from Drosophila melanogaster. Dis. Model. Mech. 9, 271-281.  https://doi.org/10.1242/dmm.023408