An interplay between immune response and neurodegenerative disease progression: An assessment using Drosophila as a model

Dhankhar, Jyoti; Agrawal, Namita; Shrivastava, Anju

doi:10.1016/j.jneuroim.2020.577302

Cited by 13 publications

(8 citation statements)

References 132 publications

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“…Similar to a central processing unit of the computer, the brain and nervous system control various biological processes, including development, metabolism and immune responses. In fact, the brain is immune-privileged and can respond to injury, infection and neurodegenerative disease through multiple innate immunity-related signaling pathways (210,211). For instance, in the adult Drosophila brain, ZIKA virus induces the activation of the Imd signaling pathway.…”

Section: The Brain and Nervous Systemmentioning

confidence: 99%

Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues

Luo

et al. 2022

Front. Immunol.

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The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit fly Drosophila melanogaster employs multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi. Drosophila has been shown to be a powerful in vivo model for studying the mechanism of innate immunity and host-pathogen interactions because Drosophila and higher organisms share conserved signaling pathways and factors. Moreover, the ease with which Drosophila genetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated in Drosophila innate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration in Drosophila will help us better study human innate immunity-related diseases.

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Section: The Brain and Nervous Systemmentioning

confidence: 99%

Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues

Luo

et al. 2022

Front. Immunol.

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“…Knockout of TLR2 or TLR4 in mice improves neurological function following TBI, whereas knockout of TNFR in mice increases lesion volume following TBI (Sullivan et al 1999;Zu and Zha 2012;Laird et al 2014;Jiang et al 2018;Shi et al 2019). Because innate immune pathways are evolutionarily conserved between flies and mammals, studies of flies, which have a simpler immune system and a more extensive experimental toolbox than rodents, may provide novel insights into roles that NF-B-mediated TLR and TNFR pathways play in determining TBI outcomes (Dhankhar et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Survival Following Traumatic Brain Injury in Drosophila Is Increased by Heterozygosity for a Mutation of the NF-κB Innate Immune Response Transcription Factor Relish

et al. 2020

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Traumatic brain injury (TBI) pathologies are caused by primary and secondary injuries. Primary injuries result from physical damage to the brain, and secondary injuries arise from cellular responses to primary injuries. A characteristic cellular response is sustained activation of inflammatory pathways commonly mediated by NF-κB transcription factors. Using a Drosophila melanogaster TBI model, we previously found that the main proximal transcriptional response to primary injuries is triggered by activation of Toll and Imd innate immune response pathways that engage NF-κB factors Dif and Relish (Rel), respectively. Here, we found by mass spectrometry that Rel protein level increased in fly heads at 4-8 h after TBI. To investigate the necessity of Rel for secondary injuries, we generated a null allele, Reldel, by CRISPR/Cas9 editing. When heterozygous but not homozygous, the Reldel mutation reduced mortality at 24 h after TBI and increased the lifespan of injured flies. Additionally, the effect of heterozygosity for Reldelon mortality was modulated by genetic background and diet. To identify genes that facilitate effects of Reldel on TBI outcomes, we compared genome-wide mRNA expression profiles of uninjured and injured +/+, +/Reldel, and Reldel/Reldel flies at 4 h following TBI. Only a few genes changed expression more than two-fold in +/Reldel flies relative to +/+ and Reldel/Reldel flies, and they were not canonical innate immune response genes. Therefore, Rel is necessary for TBI-induced secondary injuries but in complex ways involving Rel gene dose, genetic background, diet, and possibly small changes in expression of innate immune response genes.

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“…Thus, transgenic models of both species were developed [ 177 , 178 ]. Moreover, Drosophila possesses forms of innate [ 179 ] and adaptive immunity [ 180 ], making it a suitable model for studying neuroimmune dynamics in AD and PD [ 181 ]. On the contrary, C. elegance lacks inflammatory cells, microglia, and astrocytes, meaning that only aspects unrelated to neuroinflammation can be investigated using this model [ 182 , 183 ].…”

Section: In Vitro and Preclinical Studies For Alzheimer’s And Parkins...mentioning

confidence: 99%

Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases

Balestri,

Sharma,

da Silva

et al. 2024

J Neuroinflammation

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Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain’s resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

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An interplay between immune response and neurodegenerative disease progression: An assessment using Drosophila as a model

Cited by 13 publications

References 132 publications

Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues

Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues

Survival Following Traumatic Brain Injury in Drosophila Is Increased by Heterozygosity for a Mutation of the NF-κB Innate Immune Response Transcription Factor Relish

Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases

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