Stress induction of a cellular immune response in Drosophila

果蝇细胞免疫反应的应激诱导

• 批准号: 9206448
• 负责人: ROBERT A. SCHULZ
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-15 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9206448
• 关键词: Address; Animal Model; Animals; Belief; Biological Models; Blood Cells; Cell Differentiation process; Cells; Chemicals; Communication; Complement; Data; Development; Developmental Process; Drosophila genus; Employee Strikes; Enhancers; Event; Exposure to; Genes; Genetic; Genetic study; Germ Lines; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Hemocytes; Homeostasis; Human; Immune; Immune response; Immune system; Innate Immune System; Invertebrates; Investigation; Larva; Maintenance; Mammals; Marble; Mechanical Stress; Modeling; Molecular; Monitor; Nature; Nematoda; Nociception; Organ; Pain; Painless; Peripheral Nervous System; Phase; Phenotype; Process; Production; RNA interference screen; Regulation; Reporter; Research; Risk Factors; Sensory; Sensory Process; Signal Pathway; Signal Transduction; Stimulus; Stress; System; Transcriptional Regulation; Transgenic Organisms; Vertebrates; Wasps; Work; avoidance behavior; base; cell type; human disease; insight; lymph nodes; mutant; novel; pathogen; programs; public health relevance; response; smoothened signaling pathway; stem cell biology; stem-like cell; transcription factor; ultraviolet irradiation

 DESCRIPTION (provided by applicant): Nociception is the sensory process that allows animals to detect and avoid potentially harmful stimuli. This escape response appears universal in metazoans, being observed in non-mammalian and mammalian vertebrates including humans, also in invertebrates such as nematodes and fruit flies. Drosophila has emerged as a powerful system to study the genetics of nociception, due largely to the development of several pain administration and avoidance paradigms. Hazardous stimuli known to trigger nociception sensory transduction include noxious heat, noxious chemicals, UV-irradiation, and harsh mechanical stress. Drosophila has also emerged as an excellent system to study the cellular and genetic bases of hematopoiesis, including immune cell induction. Blood cell formation is a conserved developmental process and several parallels exist between hematopoiesis in this model organism and humans. The discovery of a stem cell-like hematopoietic progenitor niche in Drosophila represents a highly-significant contribution of this model system to the study of stem cell biology. Compelling data exist to support the belief that the posterior signaling center (PSC) functions as the niche within the larval lymph gland, with this domain essential for maintaining normal blood cell homeostasis. Communication between the PSC and prohemocytes present in the lymph gland medullary zone is crucial for controlling the decision as to maintaining a pluri-potent state versus initiating a hemocyte differentiation program. Such lymph gland cellular organization and molecular signaling is remarkably similar to that observed in the hematopoietic stem cell niches of several mammals. What brings together the vital processes of nociception and immune cell production is our recent discovery that mechanical stress administered to Drosophila larvae results in a robust induction of hemocyte differentiation within the lymph gland hematopoietic organ. This striking change in blood cell homeostasis includes the prodigious production of lamellocytes, cells normally induced as a protective cellular immune response to wasp pathogen introduction into a larval host. It is noteworthy that our preliminary findings suggest that lamellocyte induction occurs via different mechanisms in response to mechanical stress administration versus parasitic wasp infestation. Two Specific Aims are proposed to better comprehend the nature of mechanical stress induction of this cellular immune response. We plan to (1) investigate if genes known to function in pain avoidance behavior are also required for the cellular immune response to larval mechanical stress, and (2) identify the signaling pathway(s) regulating the cellular immune response to animal mechanical stress. Together, these approaches will allow for the use of Drosophila as a valuable model to investigate the evolutionarily conserved genetics of pain sensing and avoidance, while also addressing mechanisms controlling immune cell induction due to stress exposure.



项目成果

The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization.

果蝇幼虫对黄蜂寄生的细胞免疫反应需要伤害感受基因 painless 和 Piezo。

• DOI: 10.1016/j.bbrc.2017.03.116
• 发表时间: 2017
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Tokusumi,Yumiko;Tokusumi,Tsuyoshi;Schulz,RobertA
• 通讯作者: Schulz,RobertA

Screening and Analysis of Janelia FlyLight Project Enhancer-Gal4 Strains Identifies Multiple Gene Enhancers Active During Hematopoiesis in Normal and Wasp-Challenged Drosophila Larvae.

• DOI: 10.1534/g3.116.034439
• 发表时间: 2017-02-09
• 期刊: G3 (Bethesda, Md.)
• 作者: Tokusumi T;Tokusumi Y;Brahier MS;Lam V;Stoller-Conrad JR;Kroeger PT;Schulz RA
• 通讯作者: Schulz RA

The mir-7 and bag of marbles genes regulate Hedgehog pathway signaling in blood cell progenitors in Drosophila larval lymph glands.

• DOI: 10.1002/dvg.23210
• 发表时间: 2018-05
• 期刊: Genesis (New York, N.Y. : 2000)
• 作者: Tokusumi T;Tokusumi Y;Schulz RA
• 通讯作者: Schulz RA