Immunity-longevity tradeoff neurally controlled by GABAergic transcription factor PITX1/UNC-30

Otarigho, Benson; Aballay, Alejandro

doi:10.1016/j.celrep.2021.109187

Cited by 16 publications

(5 citation statements)

References 110 publications

(143 reference statements)

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“…NPR-15 seems to suppress specific immune genes while activating pathogen avoidance behavior to minimize potential tissue damage and the metabolic energy cost associated with activating the molecular immune response against pathogen infections. Overall, the control of immune activation is essential for maintaining homeostasis and preventing excessive tissue damage caused by an overly aggressive and energy-costly response against pathogens (60)(61)(62)(63).…”

Section: Discussionmentioning

confidence: 99%

“…Rescued strain npr-15(tm12539);Pnpr-15::npr-15 , neuronal rescued strain npr-15(tm12539);Prab-3::npr-15 and npr-15 rescued in ASJ neuron-specific, npr-15(tm12539);Ptrx-1::npr-15 were generated as described below. The ASG(-) ablated Ex[Ptax-2::CZ::ced-3(p17)::unc-54 3’UTR + Plim-6::ced-3(p15)-NZ::unc-54 3’UTR, pRF4] was generated from our previous project (61). The strains were crossed with the WT laboratory N2.…”

Section: Methodsmentioning

confidence: 99%

“…Longevity assays were performed on NGM plates containing live, UV-killed E. coli strains HT115 or OP50 as described earlier (20, 36, 61, 73). Animals were scored as alive, dead, or gone each day.…”

Section: Methodsmentioning

confidence: 99%

“…Bristol) Wild-type (WT) was used as control unless otherwise indicated. C. elegans strains RB1429 npr-15(ok1626), CX14394 npr-5(ok1583), RB1836 npr-14(ok2375), RB1289 npr-18(ok1388), RB1405 npr-22(ok1598), VC2526 npr-35(ok3258), (61). The strains were crossed with the WT laboratory N2.…”

Section: Elegans Strains and Growth Conditionsmentioning

confidence: 99%

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Neuronal NPR-15 modulates molecular and behavioral immune responses via the amphid sensory neuron-intestinal axis inC. elegans

Otarigho

Butts

Aballay

2023

Preprint

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The survival of hosts during infections relies on their ability to mount effective molecular and behavioral immune responses. Despite extensive research on these defense strategies in various species, including the model organism Caenorhabditis elegans, the neural mechanisms underlying their interplay remain poorly understood. Previous studies have highlighted the role of neural G protein-coupled receptors (GPCRs) in regulating both immunity and pathogen avoidance, which is particularly dependent on aerotaxis. To address this knowledge gap, we conducted a screen of mutants in neuropeptide receptor family genes. We found that loss-of-function mutations in npr-15 activated immunity while suppressing pathogen avoidance behavior. Through further analysis, NPR-15 was found to regulate immunity by modulating the activity of key transcription factors, namely GATA/ELT-2 and TFEB/HLH-30. Surprisingly, the lack of pathogen avoidance of npr-15 mutant animals was not influenced by oxygen levels. Moreover, our studies revealed that the amphid sensory neuron ASJ is involved in mediating the immune and behavioral responses orchestrated by NPR-15. Additionally, NPR-15 was found to regulate avoidance behavior via the TRPM gene, GON-2, which may sense the intestinal distension caused by bacterial colonization to elicit pathogen avoidance. Overall, this study expands our knowledge of how neuronal GPCRs can simultaneously modulate immunity and behavior. Given the conserved nature of the GPCR and immune signaling pathways studied, the findings contribute to a broader understanding of host defense strategies and mechanism underlining the interplay between immunity and behavior across species.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Elegans Strains and Growth Conditionsmentioning

confidence: 99%

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Neuronal NPR-15 modulates molecular and behavioral immune responses via the amphid sensory neuron-intestinal axis inC. elegans

Otarigho

Butts

Aballay

2023

Preprint

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“…In addition to being regulated by insulin-like peptides, there is growing evidence for a regulatory role for the neurotransmitter GABA in the control of the DAF-16/FOXO pathway (24), and of PMK-1/p38, perhaps as part of a biological trade-off between immunity and longevity (25). One can imagine that these regulatory connections that link food intake, immunity and ageing also reflect the complex and changing environment in which C. elegans exists in nature (26), and there is increasing experimental evidence to support this idea (27,28).…”

Section: From Germline Integrity To Organismal Resiliencementioning

confidence: 99%

An integrated view of innate immune mechanisms in C. elegans

Harding

Ewbank

2021

Biochemical Society Transactions

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The simple notion ‘infection causes an immune response' is being progressively refined as it becomes clear that immune mechanisms cannot be understood in isolation, but need to be considered in a more global context with other cellular and physiological processes. In part, this reflects the deployment by pathogens of virulence factors that target diverse cellular processes, such as translation or mitochondrial respiration, often with great molecular specificity. It also reflects molecular cross-talk between a broad range of host signalling pathways. Studies with the model animal C. elegans have uncovered a range of examples wherein innate immune responses are intimately connected with different homeostatic mechanisms, and can influence reproduction, ageing and neurodegeneration, as well as various other aspects of its biology. Here we provide a short overview of a number of such connections, highlighting recent discoveries that further the construction of a fully integrated view of innate immunity.

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