Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microbial Colonization Activates an Immune Fight-and-Flight Response via Neuroendocrine Signaling.

ABSTRACT: The ability to distinguish harmful and beneficial microbes is critical for the survival of an organism. Here, we show that bloating of the intestinal lumen of Caenorhabditis elegans caused by microbial colonization elicits a microbial aversion behavior. Bloating of the intestinal lumen also activates a broad innate immune response, even in the absence of bacterial pathogens or live bacteria. Neuroendocrine pathway genes are upregulated by intestinal bloating and are required for microbial aversion behavior. We propose that microbial colonization and bloating of the intestine may be perceived as a danger signal that activates an immune fight-and-flight response. These results reveal how inputs from the intestine can aid in the recognition of a broad range of microbes and modulate host behavior via neuroendocrine signaling.

SUBMITTER: Singh J

PROVIDER: S-EPMC6456415 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Microbial Colonization Activates an Immune Fight-and-Flight Response via Neuroendocrine Signaling.

Singh Jogender J Aballay Alejandro A

Developmental cell 20190228 1

The ability to distinguish harmful and beneficial microbes is critical for the survival of an organism. Here, we show that bloating of the intestinal lumen of Caenorhabditis elegans caused by microbial colonization elicits a microbial aversion behavior. Bloating of the intestinal lumen also activates a broad innate immune response, even in the absence of bacterial pathogens or live bacteria. Neuroendocrine pathway genes are upregulated by intestinal bloating and are required for microbial aversi ...[more]

PMID: 30827896

Similar Datasets

Fight or flight? - Flight increases immune gene expression but does not help to fight an infection.

Project description:Flight represents a key trait in most insects, being energetically extremely demanding, yet often necessary for foraging and reproduction. Additionally, dispersal via flight is especially important for species living in fragmented landscapes. Even though, based on life-history theory, a negative relationship may be expected between flight and immunity, a number of previous studies have indicated flight to induce an increased immune response. In this study, we assessed whether induced immunity (i.e. immune gene expression) in response to 15-min forced flight treatment impacts individual survival of bacterial infection in the Glanville fritillary butterfly (Melitaea cinxia). We were able to confirm previous findings of flight-induced immune gene expression, but still observed substantially stronger effects on both gene expression levels and life span due to bacterial infection compared to flight treatment. Even though gene expression levels of some immunity-related genes were elevated due to flight, these individuals did not show increased survival of bacterial infection, indicating that flight-induced immune activation does not completely protect them from the negative effects of bacterial infection. Finally, an interaction between flight and immune treatment indicated a potential trade-off: flight treatment increased immune gene expression in naïve individuals only, whereas in infected individuals no increase in immune gene expression was induced by flight. Our results suggest that the up-regulation of immune genes upon flight is based on a general stress response rather than reflecting an adaptive response to cope with potential infections during flight or in new habitats.

| S-EPMC5347902 | biostudies-literature

Fight or flight: the ethics of emergency physician disaster response.

Project description:Most disaster plans depend on using emergency physicians, nurses, emergency department support staff, and out-of-hospital personnel to maintain the health care system's front line during crises that involve personal risk to themselves or their families. Planners automatically assume that emergency health care workers will respond. However, we need to ask: Should they, and will they, work rather than flee? The answer involves basic moral and personal issues. This article identifies and examines the factors that influence health care workers' decisions in these situations. After reviewing physicians' response to past disasters and epidemics, we evaluate how much danger they actually faced. Next, we examine guidelines from medical professional organizations about physicians' duty to provide care despite personal risks, although we acknowledge that individuals will interpret and apply professional expectations and norms according to their own situation and values. The article goes on to articulate moral arguments for a duty to treat during disasters and social crises, as well as moral reasons that may limit or override such a duty. How fear influences behavior is examined, as are the institutional and social measures that can be taken to control fear and to encourage health professionals to provide treatment in crisis situations. Finally, the article emphasizes the importance of effective risk communication in enabling health care professionals and the public to make informed and defensible decisions during disasters. We conclude that the decision to stay or leave will ultimately depend on individuals' risk assessment and their value systems. Preparations for the next pandemic or disaster should include policies that encourage emergency physicians, who are inevitably among those at highest risk, to "stay and fight."

| S-EPMC7124291 | biostudies-literature

Fight or flight cardiac responses require augmentation of Ca2+ influx via Rad phosphorylation [RNAseq]

Project description:One of the most recognizable physiological phenomena is the adrenergic-induced fight-or-flight increase in heart rate and cardiac contraction. For the β-adenergic agonist-induced enhancement of calcium influx and transients, and contractility in the heart, we identify the dual requirement of a subpopulation of Rad-bound calcium channels under basal conditions and PKA phosphorylation of Rad. In mice expressing a non-phosphorylatable Rad mutant, basal cardiac contractility is reduced and adrenergic-augmentation of the calcium current and contractility are disabled. Expression of mutant calcium channel β-subunits that cannot bind the mutant Rad restored contractility, revealing a highly specific therapeutic approach to mimic the contractility imparted by adrenergic agonists. Our findings place Rad and its modulation of calcium channels at the nexus of adrenergic modulation of cardiac responses.

2022-03-20 | GSE198903 | GEO

The fight-or-flight response is associated with PBMC expression profiles related to immune defence and recovery in swine.

Project description:Defining phenotypes according to molecular features would promote the knowledge of functional traits like behaviour in both human and animal research. Beside physiological states or environmental factors, an innate predisposition of individual coping strategies was discussed, including the proactive and reactive pattern. According to backtest reactivity, animals assigned as high-resisting (proactive) and low-resisting (reactive) were immune challenged with tetanus toxoid in a time course experiment. Using the Affymetrix platform and qPCR, individual coping characteristics were reflected as gene expression signatures in porcine peripheral blood mononuclear cells (PBMC) at naïve state (day 0) and in response to the model antigen (day 14, day 28, and day 140). Further, the blood cell count was analysed at all stages. On the transcriptional level, processes acting on cell communication, vasculogenesis, and blood coagulation were highlighted in high-resisting animals at naïve state (day 0), temporarily blurred due to immune challenge (day 14) but subsequently restored and intensified (day 28). Notably, similar amounts of white and red blood cells, platelets and haematocrit between high-resisting and low-resisting samples suggest coping-specific expression patterns rather than alterations in blood cell distribution. Taken together, the gene expression patterns indicate that proactive pigs might favour molecular pathways enabling an effective strategy for defence and recovery. This corroborates the previously suggested belief, that proactive animals are prone to an increased number of injuries as an evolutionary inherited mechanism. In contrast to previous assumptions, coping-specific immunity in pigs lacks inherited shifts between cellular and humoral immune responses.

| S-EPMC4368799 | biostudies-literature

Molecular mechanism of calcium channel regulation in the fight-or-flight response.

Project description:During the fight-or-flight response, the sympathetic nervous system stimulates L-type calcium ion (Ca2+) currents conducted by Ca(V)1 channels through activation of ?-adrenergic receptors, adenylyl cyclase, and phosphorylation by adenosine 3',5'-monophosphate-dependent protein kinase [also known as protein kinase A (PKA)], increasing contractility of skeletal and cardiac muscles. We reconstituted this regulation of cardiac Ca(V)1.2 channels in non-muscle cells by forming an autoinhibitory signaling complex composed of Ca(V)1.2?1800 (a form of the channel truncated at the in vivo site of proteolytic processing), its noncovalently associated distal carboxyl-terminal domain, the auxiliary ???? and ?(2b) subunits, and A-kinase anchoring protein 15 (AKAP15). A factor of 3.6 range of Ca(V)1.2 channel activity was observed from a minimum in the presence of protein kinase inhibitors to a maximum upon activation of adenylyl cyclase. Basal Ca(V)1.2 channel activity in unstimulated cells was regulated by phosphorylation of serine-1700 and threonine-1704, two residues located at the interface between the distal and the proximal carboxyl-terminal regulatory domains, whereas further stimulation of channel activity through the PKA signaling pathway only required phosphorylation of serine-1700. Our results define a conceptual framework for Ca(V)1.2 channel regulation and identify sites of phosphorylation that regulate channel activity.

| S-EPMC3063709 | biostudies-literature

A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage

Project description:To protect themselves from the constant threat of bacteriophage (phage) infection, bacteria have evolved diverse immune systems including restriction-modification, CRISPR-Cas, and many others. Here we describe the discovery of a two-protein transcriptional regulator module associated with hundreds of CBASS immune systems, and demonstrate that this module drives expression of its associated CBASS system in response to DNA damage. We show that the helix-turn-helix transcriptional repressor CapH binds the promoter region of its associated CBASS system to repress transcription until it is cleaved by the metallopeptidase CapP. CapP is activated in vitro by single-stranded DNA, and in cells by DNA-damaging drugs. Together, CapH and CapP drive increased expression of their associated CBASS system in response to DNA damage. We identify CapH and CapP-related proteins associated with diverse known and putative bacterial immune systems including DISARM and Pycsar anti-phage operons. Overall, our data highlight a mechanism by which bacterial immune systems can sense and respond to a universal signal of cell stress, potentially enabling multiple immune systems to mount a coordinated defensive response against an invading pathogen.

| S-SCDT-EMBOJ-2022-111540 | biostudies-other

Fight-or-flight responses require augmentation of Ca2+ influx via Rad phosphorylation

Project description:Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. Despite decades of investigations, predominantly focusing on ryanodine receptor and phospholamban phosphorylation, the molecular mechanisms underlying the sympathetic nervous system control of cardiac contractility remain controversial and incompletely elucidated. Here, we identify the calcium-channel inhibitor Rad as a critical component. In cardiomyocytes isolated from knock-in mice expressing Rad with alanine-substitutions of the four PKA-phosphorylated serine residues (4SA-Rad), calcium currents cannot be increased by adrenergic agonists or phosphatase inhibitor. In these mice, basal cardiac contractility, exercise capacity and heart rate are reduced, and the augmentation of contractile force by adrenergic agonists is severely blunted. Expression of mutant calcium-channel β-subunits that cannot bind Rad is sufficient to restore calcium influx and cardiac contractility in 4SA-Rad mice to levels induced by adrenergic agonists in wild-type mice, revealing a potential therapeutic approach to enhance cardiac contractility while bypassing stimulation of adrenergic receptors.

2022-09-26 | PXD033492 | Pride

Phosphorylation of the ryanodine receptor mediates the cardiac fight or flight response in mice.

Project description:During the classic "fight-or-flight" stress response, sympathetic nervous system activation leads to catecholamine release, which increases heart rate and contractility, resulting in enhanced cardiac output. Catecholamines bind to ?-adrenergic receptors, causing cAMP generation and activation of PKA, which phosphorylates multiple targets in cardiac muscle, including the cardiac ryanodine receptor/calcium release channel (RyR2) required for muscle contraction. PKA phosphorylation of RyR2 enhances channel activity by sensitizing the channel to cytosolic calcium (Ca²+). Here, we found that mice harboring RyR2 channels that cannot be PKA phosphorylated (referred to herein as RyR2-S2808A+/+ mice) exhibited blunted heart rate and cardiac contractile responses to catecholamines (isoproterenol). The isoproterenol-induced enhancement of ventricular myocyte Ca²+ transients and fractional shortening (contraction) and the spontaneous beating rate of sinoatrial nodal cells were all blunted in RyR2-S2808A+/+ mice. The blunted cardiac response to catecholamines in RyR2-S2808A+/+ mice resulted in impaired exercise capacity. RyR2-S2808A+/+ mice were protected against chronic catecholaminergic-induced cardiac dysfunction. These studies identify what we believe to be new roles for PKA phosphorylation of RyR2 in both the heart rate and contractile responses to acute catecholaminergic stimulation.

| S-EPMC2993575 | biostudies-literature

Phosphorylation sites required for regulation of cardiac calcium channels in the fight-or-flight response.

Project description:L-type Ca(2+) currents conducted by CaV1.2 channels initiate excitation-contraction coupling in the heart. Their activity is increased by ?-adrenergic/cAMP signaling via phosphorylation by PKA in the fight-or-flight response, but the sites of regulation are unknown. We describe the functional role of phosphorylation of Ser1700 and Thr1704-sites of phosphorylation by PKA and casein kinase II at the interface between the proximal and distal C-terminal regulatory domains. Mutation of both residues to Ala in STAA mice reduced basal L-type Ca(2+) currents, due to a small decrease in expression and a substantial decrease in functional activity. The increase in L-type Ca(2+) current caused by isoproterenol was markedly reduced at physiological levels of stimulation (3-10 nM). Maximal increases in calcium current at nearly saturating concentrations of isoproterenol (100 nM) were also significantly reduced, but the mutation effects were smaller, suggesting that alternative regulatory mechanisms are engaged at maximal levels of stimulation. The ?-adrenergic increase in cell contraction was also diminished. STAA ventricular myocytes exhibited arrhythmic contractions in response to isoproterenol, and up to 20% of STAA cells failed to sustain contractions when stimulated at 1 Hz. STAA mice have reduced exercise capacity, and cardiac hypertrophy is evident at 3 mo. We conclude that phosphorylation of Ser1700 and Thr1704 is essential for regulation of basal activity of CaV1.2 channels and for up-regulation by ?-adrenergic signaling at physiological levels of stimulation. Disruption of phosphorylation at those sites leads to impaired cardiac function in vivo, as indicated by reduced exercise capacity and cardiac hypertrophy.

| S-EPMC3845157 | biostudies-literature

Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling.

Project description:The toll-like receptor (TLR) family comprises both cell-surface and intracellular receptors that recognize different types of pathogen-associated molecular patterns (PAMPs) leading to the production of pro-inflammatory cytokines and subsequent development of adaptive immunity. TLR2 is a cell-surface receptor initially thought to act as a bacterial sentinel but also shown to recognize a number of viral glycoproteins. In this study, we sought to characterize the role of TLR2 in the activation of the immune response by peste des petits ruminants virus (PPRV), a morbillivirus of the Paramixoviridae family that causes an acute, highly contagious disease in goats and sheep. Using human embryonic kidney (HEK) 293 cells stably expressing human (h)TLR2 but lacking any other TLR, we found that PPRV induces IL-8 production in a dose-dependent manner. That activation is only observed in cells expressing hTLR2 and is greatly reduced when the receptor is blocked by pretreatment with specific antibody. We identified hemagglutinin (H) as the viral protein responsible of TLR2 activation by performing the same assays with purified recombinant mammalian-expressed H protein. Exogenous addition of recombinant H protein to cell culture induces high levels of interleukin (IL)-8 only in TLR2-expressing cells. Moreover, H engagement on TLR2 in the monocytic cell line THP-1 activates extracellular-signal-regulated kinase (ERK) signaling. Stimulation of primary ovine dendritic cells with either inactivated PPRV or purified recombinant H protein results in transcription of pro-inflammatory cytokines and the secretion of the Th1-polarizing cytokine IL-12. The role of these host immune mechanisms in the control of PPR is discussed.

| S-EPMC7889028 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data