Immune Receptor Signaling and the Mushroom Body Mediate Post-ingestion Pathogen Avoidance

Kobler, Johanna M.; Jiménez, Francisco; Petcu, Irina; Kadow, Ilona C. Grunwald

doi:10.1016/j.cub.2020.09.022

Cited by 42 publications

(51 citation statements)

References 86 publications

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“…Immune activation has been shown to affect a range of behaviours and physiological functions including sleep, reproduction, cognition and metabolism (An and Waldman, 2016; Chambers et al, 2012; Dionne et al, 2006; Kobler et al, 2020; Kuo et al, 2010; Mallon et al, 2014; Shirasu-Hiza et al, 2007; Vincent and Sharp, 2014). Infection-induced changes in the host are often thought to be of benefit to either the host or the pathogen.…”

Section: Discussionmentioning

confidence: 99%

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster

Vincent

Beckwith

Pearson

et al. 2021

Preprint

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Host behavioural changes are among the most apparent effects of infection. ‘Sickness behaviour’ can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here we use a real-time tracking and behavioural profiling platform to show that, in Drosophila melanogaster, many systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in several lethal infections. Using various bacteria and D. melanogaster immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with Micrococcus luteus, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the Toll ligand spätzle and Toll-pathway activity in the fat body and the brain. In contrast, increased activity after infection with Francisella novicida, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of either spätzle or the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response.

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Section: Discussionmentioning

confidence: 99%

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster

Vincent

Beckwith

Pearson

et al. 2021

Preprint

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“…Interestingly, PGRPs, which are the receptors that sense pathogens, were recently shown to be required in octopamine neurons in order to behaviorally avoid pathogenic bacteria in Drosophila [162]. Octopamine neurons are required for a number of social behaviors including aggression and courtship in Drosophila [163], crickets [164], and ants [165].…”

Section: Discussionmentioning

confidence: 99%

“…While unravelling the link between behavior and neuroimmune signaling is challenging, we hypothesize that the increased social interaction in conjunction with increased innate immune gene expression that we observe is consistent with the notion that the neuroimmune signaling system regulates anxiety behaviors. Interestingly, PGRPs, which are the receptors that sense pathogens, were recently shown to be required in octopamine neurons in order to behaviorally avoid pathogenic bacteria in Drosophila [162]. Octopamine neurons are required for a number of social behaviors including aggression and courtship in Drosophila [163], crickets [164], and ants [165].…”

Section: Social Behavior and Immune Responsementioning

confidence: 99%

Neuromolecular and behavioral effects of ethanol deprivation inDrosophila

D'Silva

McCullar

Conard

et al. 2021

Preprint

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Alcohol use disorder (AUD) is characterized by loss of control in limiting alcohol intake. This may involve intermittent periods of abstinence followed by alcohol seeking and, consequently, relapse. However, little is understood of the molecular mechanisms underlying the impact of alcohol deprivation on behavior. Using a new Drosophila melanogaster repeated intermittent alcohol exposure model, we sought to identify how ethanol deprivation alters spontaneous behavior, determine the associated neural structures, and reveal correlated changes in brain gene expression. We found that repeated intermittent ethanol-odor exposures followed by ethanol-deprivation dynamically induces behaviors associated with a negative affect state. Although behavioral states broadly mapped to many brain regions, persistent changes in social behaviors mapped to the mushroom body and surrounding neuropil. This occurred concurrently with changes in expression of genes associated with sensory responses, neural plasticity, and immunity. Like social behaviors, immune response genes were upregulated following three-day repeated intermittent ethanol-odor exposures and persisted with one or two days of ethanol-deprivation, suggesting an enduring change in molecular function. Our study provides a framework for identifying how ethanol deprivation alters behavior with correlated underlying circuit and molecular changes.

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“…We speculate that he γ5β′2a/β′2mp/β′2mp_bilateral MBONs are activated by physiological or environmental factors that reduce sleep in response to competing motivational drives, with ban expression acting as the switch to turn neural activity off and on. These MBON neurons are known to be required for behaviors that might compete with sleep, including avoidance of aversive stimuli, aversion to pathogen-infected food, ingestion, startle-induced locomotion, and memory for visual and olfactory cues (Al-Anzi and Zinn, 2018; Aso et al, 2014b; Kobler et al, 2020; Lewis et al, 2015; Owald et al, 2015; Sun et al, 2018; Yamazaki et al, 2018). For the γ5β′2a/β′2mp/β′2mp_bilateral MBONs, recruitment into the sleep circuitry likely also involves dopaminergic signaling since RNAi knockdown of the DopR1 and DopR2 dopamine receptors in these cells lead to an increase in nighttime sleep (Driscoll et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Bantam regulates the adult sleep circuit in Drosophila

Hobin

Dorfman

Adel

et al. 2021

Preprint

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Sleep is a highly conserved feature of animal life characterized by dramatic changes in behavior, neural physiology and gene expression. The gene regulatory factors responsible for these sleep-dependent changes remain largely unknown. microRNAs are post-transcriptional modulators of gene expression which have been implicated in sleep regulation. Our previous screen identified 25 sleep-regulating microRNAs in Drosophila melanogaster, including the developmental regulator bantam (ban). Here we show that ban promotes early nighttime sleep through a population of glutamatergic neurons- the γ5β′2a/β′2mp/β′2mp_bilateral Mushroom Body Output Neurons (MBONs). We found that knockdown of ban in these neurons led to a reduction in early night sleep. The γ5β′2a/β′2mp/β′2mp_bilateral MBONs were previously shown to be wake-promoting, suggesting that ban acts to inhibit these neurons. GCaMP calcium imaging revealed that bantam inhibits the neural activity of the γ5β′2a/β′2mp/β′2mp_bilateral MBONs during the night but not the day. Blocking synaptic transmission in the γ5β′2a/β′2mp/β′2mp_bilateral MBONs rescued the effect of ban knockdown on sleep. Together these results suggest that ban promotes night sleep via the inhibition of the γ5β′2a/β′2mp/β′2mp_bilateral MBONs. RNAseq further revealed that bantam negatively regulates the wake-promoting mRNAs Kelch and CCHamide-2 receptor in the γ5β′2a/β′2mp/β′2mp_bilateral MBONs. These experiments establish bantam as an active regulator of sleep and neural activity within the fly brain.

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Immune Receptor Signaling and the Mushroom Body Mediate Post-ingestion Pathogen Avoidance

Cited by 42 publications

References 86 publications

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster

Neuromolecular and behavioral effects of ethanol deprivation inDrosophila

Bantam regulates the adult sleep circuit in Drosophila

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