Abstract

Innate immunity is the first line of defense against invading pathogens and plays an essential role in defending the brain against infection, injury, and disease. It is currently well recognized that central nervous system (CNS) infections can result in long-lasting neurological sequelae and that innate immune and inflammatory reactions are highly implicated in the pathogenesis of neurodegeneration. Due to the conservation of the mechanisms that govern neural development and innate immune activation from flies to mammals, the lack of a classical adaptive immune system and the availability of numerous genetic and genomic tools, the fruit fly Drosophila melanogaster presents opportunities to investigate the cellular and molecular mechanisms associated with immune function in brain tissue and how they relate to infection, injury and neurodegenerative diseases. Here, we present an overview of currently identified innate immune mechanisms specific to the adult Drosophila brain.

Highlights

  • Innate immunity represents the first line of defense against microbial invaders and plays a significant role in limiting pathogen spread as well as in activating the long-lasting adaptive immunity [1,2]

  • In this review we summarize recent studies of innate immunity with focus on brain immune reactions, how they relate to pathological conditions such as neurodegeneration, and neuroprotection in the context of aging, brain injury, and infection

  • In addition to these three types of immunity, proteolytic cascades contribute to melanization and coagulation reactions following wounding [43] and RNA interference (RNAi), inducible responses, as well as intrinsic immunity based on the action of restriction factors protect against virus infection [30]

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Summary

Introduction

Innate immunity represents the first line of defense against microbial invaders and plays a significant role in limiting pathogen spread as well as in activating the long-lasting adaptive immunity [1,2]. Within the central nervous system (CNS), infections are a source of significant mortality worldwide and can lead to long-lasting neurological sequelae in surviving individuals [4,5] These infections can be caused by a plethora of pathogens, including bacteria and viruses, and can lead to acute manifestations such as meningitis [6] and encephalitis [7,8], or chronic neurodegenerative conditions such as Alzheimer’s disease [9,10]. Protection against neurotropic viruses that replicate in the CNS relies on local innate immune responses mediated by the activation of Interferon (IFN) regulatory factors (IRFs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling cascades and their downstream effectors [14] These responses, which are mounted by neural cell types including microglia, astrocytes and neurons, use pattern recognition receptors (PRRs) to detect pathogen invasion and induce protective neuroinflammation [5,14]. In this review we summarize recent studies of innate immunity with focus on brain immune reactions, how they relate to pathological conditions such as neurodegeneration, and neuroprotection in the context of aging, brain injury, and infection

Innate Immune Reactions and Pathways in the Brain
NF-κB Signaling Pathways
Autophagy
Phagocytosis
RNA Interference
Regulation of Innate Immunity in the Brain
Findings
Concluding Remarks
Full Text
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