Systemic innate immune response induces death of olfactory receptor neurons in Drosophila.

Publisher: Blackwell Science Ltd Country of Publication: England NLM ID: 9607379 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2443 (Electronic) Linking ISSN: 13569597 NLM ISO Abbreviation: Genes Cells Subsets: MEDLINE

Original Publication: Oxford, UK : Blackwell Science Ltd., 1996-

Drosophila Proteins*/genetics ; Drosophila Proteins*/metabolism ; Olfactory Receptor Neurons*/metabolism; Animals ; Apoptosis ; Drosophila/metabolism ; Immunity, Innate

Neural functions are known to decline during normal aging and neurodegenerative diseases. However, the mechanisms of functional impairment owing to the normal aging of the brain are poorly understood. Previously, we reported that caspase-3-like protease, the protease responsible for inducing apoptosis, is activated in a subset of olfactory receptor neurons (ORNs), especially in Drosophila Or42b neurons, during normal aging. Herein, we investigated the molecular mechanism underlying age-related caspase-3-like protease activation and cell death in Or42b neurons. Gene expression profiling of young and aged fly antenna showed that the expression of antimicrobial peptides was significantly upregulated, suggesting an activated innate immune response. Consistent with this observation, inhibition or activation of the innate immune pathway caused delayed or precocious cell death, respectively, in Or42b neurons. Accordingly, autonomous cell activation of the innate immune pathway in Or42b neurons is not likely required for their age-related death, whereas the systemic innate immune response induces caspase-3-like protease activation in Or42b neurons; this indicated that the death of these neurons is regulated non-cell autonomously. We propose a possible link between the innate immune response and the death of olfactory neurons during normal aging.
(© 2021 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Buchon, N., Silverman, N., & Cherry, S. (2014). Immunity in Drosophila melanogaster-from microbial recognition to whole-organism physiology. Nature Reviews Immunology, 14, 796-810. https://doi.org/10.1038/nri3763.
Burke, S. N., & Barnes, C. A. (2006). Neural plasticity in the ageing brain. Nature Reviews Neuroscience, 7, 30-40. https://doi.org/10.1038/nrn1809.
Cao, Y., Chtarbanova, S., Petersen, A. J., & Ganetzky, B. (2013). Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain. Proceedings of the National Academy of Sciences of the United States of America, 110, E1752-E1760. https://doi.org/10.1073/pnas.1306220110.
Chen, H., Zheng, X., & Zheng, Y. (2014). Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia. Cell, 159, 829-843. https://doi.org/10.1016/j.cell.2014.10.028.
Chihara, T., Kitabayashi, A., Morimoto, M., Takeuchi, K.-I., Masuyama, K., Tonoki, A., Davis, R. L., Wang, J. W., & Miura, M. (2014). Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila. PLoS Genetics, 10(6), e1004437. https://doi.org/10.1371/journal.pgen.1004437.
Doty, R. L., & Kamath, V. (2014). The influences of age on olfaction: A review. Frontiers in Psychology, 5, 20. https://doi.org/10.3389/fpsyg.2014.00020.
Fehlbaum, P., Bulet, P., Michaut, L., Lagueux, M., Broekaert, W. F., Hetru, C., & Hoffmann, J. A. (1994). Insect immunity: Septic injury of Drosophila induces the synthesis of a potent antifungal peptide with sequence homology to plant antifungal peptides. Journal of Biological Chemistry, 269, 33159-33163. https://doi.org/10.1016/S0021-9258(20)30111-3.
Fontana, L., & Partridge, L. (2015). Promoting health and longevity through diet: From model organisms to humans. Cell, 161, 106-118. https://doi.org/10.1016/j.cell.2015.02.020.
Fontana, L., Partridge, L., & Longo, V. D. (2010). Extending healthy life span-from yeast to humans. Science, 328, 321-326. https://doi.org/10.1126/science.1172539.
Han, Z. S., & Ip, Y. T. (1999). Interaction and specificity of Rel-related proteins in regulating Drosophila immunity gene expression. Journal of Biological and Chemical Sciences, 274, 21355-21361. https://doi.org/10.1074/jbc.274.30.21355.
Hoffman, H. J., Ishii, E. K., & MacTurk, R. H. (1998). Age-related changes in the prevalence of smell/taste problems among the United States adult population. Results of the 1994 disability supplement to the National Health Interview Survey (NHIS). Annals of the New York Academy of Sciences, 855, 716-722.
Jefferis, G. S. X. E., & Hummel, T. (2006). Wiring specificity in the olfactory system. Seminars in Cell and Developmental Biology, 17, 50-65. https://doi.org/10.1016/j.semcdb.2005.12.002.
Koto, A., Kuranaga, E., & Miura, M. (2009). Temporal regulation of Drosophila IAP1 determines caspase functions in sensory organ development. Journal of Biological and Chemical Sciences, 187, 219-231. https://doi.org/10.1083/jcb.200905110.
Libert, S., Zwiener, J., Chu, X., VanVoorhies, W., Roman, G., & Pletcher, S. D. (2007). Regulation of Drosophila life span by olfaction and food-derived odors. Science, 315, 1133-1137. https://doi.org/10.1126/science.1136610.
Ligoxygakis, P., Pelte, N., Hoffmann, J. A., & Reichhart, J. M. (2002). Activation of Drosophila toll during fungal infection by a blood serine protease. Science, 297, 114-116. https://doi.org/10.1126/science.1072391.
Liu, N., Landreh, M., Cao, K., Abe, M., Hendriks, G. J., Kennerdell, J. R., Zhu, Y., Wang, L. S., & Bonini, N. M. (2012). The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature, 482, 519-523. https://doi.org/10.1038/nature10810.
Meng, X., Khanuja, B. S., & Ip, Y. T. (1999). Toll receptor-mediated Drosophila immune response requires Dif, an NF- κB factor. Genes & Development, 13, 792-797. https://doi.org/10.1101/gad.13.7.792.
Meyer, S. N., Amoyel, M., Bergantiños, C., De La Cova, C., Schertel, C., Basler, K., & Johnston, L. A. (2014). An ancient defense system eliminates unfit cells from developing tissues during cell competition. Science, 346, 1258236. https://doi.org/10.1126/science.1258236.
Petersen, A. J., Rimkus, S. A., & Wassarman, D. A. (2012). ATM kinase inhibition in glial cells activates the innate immune response and causes neurodegeneration in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 109, E656-E664. https://doi.org/10.1073/pnas.1110470109.
Pletcher, S. D., Macdonald, S. J., Marguerie, R., Certa, U., Stearns, S. C., Goldstein, D. B., & Partridge, L. (2002). Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster. Current Biology, 12, 712-723. https://doi.org/10.1016/S0960-9822(02)00808-4.
Potter, C. J., Tasic, B., Russler, E. V., Liang, L., & Luo, L. (2010). The Q system: A repressible binary system for transgene expression, lineage tracing, and mosaic analysis. Cell, 141, 536-548. https://doi.org/10.1016/j.cell.2010.02.025.
Schneider, D. S., Hudson, K. L., Lin, T. Y., & Anderson, K. V. (1991). Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal-ventral polarity in the Drosophila embryo. Genes & Development, 5, 797-807. https://doi.org/10.1101/gad.5.5.797.
Semmelhack, J. L., & Wang, J. W. (2009). Select Drosophila glomeruli mediate innate olfactory attraction and aversion. Nature, 459, 218-223. https://doi.org/10.1038/nature07983.
Stökl, J., Strutz, A., Dafni, A., Svatos, A., Doubsky, J., Knaden, M., Sachse, S., Hansson, B. S., & Stensmyr, M. C. (2010). A deceptive pollination system targeting drosophilids through olfactory mimicry of yeast. Current Biology, 20, 1846-1852. https://doi.org/10.1016/j.cub.2010.09.033.
Tanji, T., Yun, E. Y., & Ip, Y. T. (2010). Heterodimers of NF-κB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 107, 14715-14720. https://doi.org/10.1073/pnas.1009473107.
Tzou, P., Reichhart, J. M., & Lemaitre, B. (2002). Constitutive expression of a single antimicrobial peptide can restore wild-type resistance to infection in immunodeficient Drosophila mutants. Proceedings of the National Academy of Sciences of the United States of America, 99, 2152-2157. https://doi.org/10.1073/pnas.042411999.
Williams, D. W., Kondo, S., Krzyzanowska, A., Hiromi, Y., & Truman, J. W. (2006). Local caspase activity directs engulfment of dendrites during pruning. Nature Neuroscience, 9, 1234-1236. https://doi.org/10.1038/nn1774.

18K14716 JSPS KAKENHI; 20K15903 JSPS KAKENHI; 18H05369 JSPS KAKENHI; 20K20378 JSPS KAKENHI; 16H06385 JSPS KAKENHI; 21H04774 JSPS KAKENHI; Molecular Biology Society of Japan; Toray Science Foundation; Naito Foundation; Astellas Foundation for Research on Metabolic Disorders; Takeda Science Foundation; Frontier Development Program for Genome Editing and the Core Research for Organelle Diseases in Hiroshima University; JP17gm0610004 Japan Agency for Medical Research Development; JP21gm5010001 Japan Agency for Medical Research Development

Keywords: Drosophila; aging; apoptosis; caspase-3; cell death; innate immunity; olfactory system

0 (Drosophila Proteins)

Date Created: 20211218 Date Completed: 20220222 Latest Revision: 20220222

20231215

10.1111/gtc.12914

34921694