Caenorhabditis elegans saposin-like spp-9 is involved in specific innate immune responses

Madhu, Bhoomi; Lakdawala, Mohammed Farhan; Issac, Neethu G; Gumienny, Tina L.

doi:10.1038/s41435-020-0108-6

Cited by 8 publications

(9 citation statements)

References 64 publications

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“…Monitoring whole‐body fluorescence from two distinct DBL‐1 pathway transcriptional reporters, spp‐9p ::GFP (Roberts et al, 2010) and RAD/SMADp ::GFP::NLS (Tian et al, 2010), enabled the spatial characterization and quantification of DBL‐1 signaling to peripheral tissues. In keeping with spp‐9 expression being inversely proportional to DBL‐1 levels (Madhu et al, 2020; Roberts et al, 2010), we observed enhanced spp‐9p ::GFP fluorescence in transgenic animals expressing neural hsf‐1 (Figure 3a,b and Figure ), indicating a reduction in DBL‐1 signaling. We also observed that expression of full‐length hsf‐1 in the nervous system was sufficient to activate spp‐9 transcription in the hsf‐1(sy441) hypomorphic background (Figure ), further supporting the neuronal origins of the DBL‐1 signaling mechanism.…”

Section: Resultssupporting

confidence: 86%

Reduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevity

et al. 2022

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Rates of tissue aging within an animal are coordinated through a complex network of intra-and intercellular signaling pathways.Due to the complexity of this multifactorial aging mechanism, a variety of molecular targets have been identified as age determinates across a number of model organisms ranging from yeast to primates (Kenyon, 2010). In multicellular organisms, the ability of these molecules to act across tissues and connect organ systems plays a critical role in animal physiology and age determination. The nervous

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Section: Resultssupporting

confidence: 86%

Reduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevity

et al. 2022

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“…GO-term/Enrichment/ and analyses of the context-specific (diet) changes in transcripts between odr-1lf mutants revealed significant changes in stress responses and lipid homeostasis, similar to that observed in WT animals (Figure S6E), in fact very few differences were found in the transcriptional response to the Methylobacterium diet between WT and animals lacking functional odr-1 (Figure S6F); including the enhanced expression of genes involved in sphingosine metabolism(Figure S6G-I). These data suggest the role odr-1 plays in AWB/AWC is downstream of the induced spp-9 transcripts, which normally are most highly expressed in the intestine[56] ( Figure 6D ), which fits our model suggesting the antipathy response occurs after the Methylobacterium diet is ingested.…”

Section: Resultssupporting

confidence: 68%

C. elegansdisplay antipathy behavior towards food after contemporaneous integration of nutritional needs and dietary lipid availability

Stuhr,

Ramos,

Turner

et al. 2024

Preprint

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SUMMARYOrganisms utilize sophisticated neurocircuitry to select optimal food sources within their environment.Methylobacteriumis a lifespan-promoting bacterial diet forC. elegansthat drives faster development and longevity, however after ingestion,C. elegansconsistently choose any other food option available. A screen for genetic regulators of the avoidance behavior towardMethylobacteriumidentified the AWB and AWC sensory neurons and theodr-1guanylate cyclase expressed exclusively in those four ciliated neurons as mediators of the antipathy response. Metabolic profiling of theMethylobacteriumdiet reveals a macromolecular profile enriched in saturated fats and here we show thatC. eleganssense and integrate signals related to the type of ingested lipids that subsequently cues food-related behaviors. Moreover, disruption of endogenous lipid metabolism modifies the intensity of antipathy towardMethylobacteriumwhich suggests that the current state of lipid homeostasis influences food preference. Enhanced expression of the sphingolipid degradation enzyme Saposin/spp-9enhances antipathy behaviors and activation of the sphingosine rheostat and more specifically modulation of the bioactive lipid mediator sphingosine-1-phosphate (S1P) acts as a signal to promote avoidance ofMethylobacterium. Taken together, our work reveals thatC. elegansmodify food choices contemporaneously based on the availability of dietary lipids and the ability to metabolize dietary lipids.HIGHLIGHTSUncover new molecular mechanisms underlying the decision matrix an animal uses to choose what foods to eat.Define the molecular mechanisms underlying an antipathy behavioral response toward foods after initial ingestion that contemporaneously integrates dietary needs with nutritional profile.ODR-1 signaling from AWB and AWC ciliated neurons of theC. elegansnervous system mediate the antipathy response to diet.Manipulation of sphingosine-1-phosphate (S1P) of the sphingosine rheostat controls the intensity of the antipathy behavioral response.Modulating antipathy behaviors can impact the magnitude of the lifespan-promoting effects of longevity diets.

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“…After RNA isolation, cDNA was synthesized and quantitative real-time PCR was performed as previously described 38 . 2 µg of total RNA isolated was primed with oligo(dT) and reverse transcribed to yield cDNA using the SuperScript III reverse transcriptase kit as per manufacturer's protocol (Invitrogen).…”

Section: Cdna Synthesis and Qrt-pcrmentioning

confidence: 99%

The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses inC. elegans

Madhu

Hanson

Gumienny

2021

Preprint

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Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-β; superfamily pathway. While the role of TGF-β signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we address the role of DBL-1/TGF-β in regulating signature host defense responses to a wide range of bacteria in C. elegans. This work reveals a role of DBL-1/TGF-β in animal survival, organismal behaviors, and molecular responses in different environments. Additionally, we identify a novel role for SMA-4/Smad that suggests both DBL-1/TGF-β-dependent and -independent functions in host avoidance responses. RNA-seq analyses and immunity reporter studies indicate DBL-1/TGF-β differentially regulates target gene expression upon exposure to different bacteria. Furthermore, the DBL-1/TGF-β pathway is itself differentially affected by the bacteria exposure. Collectively, these findings demonstrate bacteria-specific host immune responses regulated by the DBL-1/TGF-β signaling pathway.

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Caenorhabditis elegans saposin-like spp-9 is involved in specific innate immune responses

Cited by 8 publications

References 64 publications

Reduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevity

Reduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevity

C. elegansdisplay antipathy behavior towards food after contemporaneous integration of nutritional needs and dietary lipid availability

The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses inC. elegans

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