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Otarigho, B.

Publications and source records attributed to Otarigho, B..

4 recordsLinked to original sources

NMDA Receptor Subunit NMR-2 Regulates Pathogen-Induced Immune Responses via the Nervous System in C. elegans

Neural control of innate immunity must balance restraint of basal immune activity with rapid activation upon pathogen encounter. Glutamate, the primary excitatory neurotransmitter in the nervous system, has been implicated in several neurological disorders associated with inflammation, suggesting a potential link to immune regulation. However, how glutamatergic signaling contributes to immune balance remains unknown. Here, we demonstrated that the NMDA-type ionotropic glutamate receptor subunit NMR-2, a component of the NMDA receptor complex, acts in the C. elegans nervous system as a key regulator of pathogen-induced immune responses. Loss of nmr-2 enhanced resistance to Staphylococcus aureus and Pseudomonas aeruginosa, without elevating basal immune gene expression. The pathogen-induced response controlled by NMR-2 required the conserved PMK-1/p38 MAPK, DAF-16/FOXO, and HLH-30/TFEB pathways. We identified the AVD interneuron as the site of action of NMR-2, where it integrates inputs from upstream sensory neurons ASE, ASK, AQR, and PQR. These findings uncover a neural circuit in which glutamatergic signaling distinguishes basal immune gene expression from pathogen-induced immune responses, revealing a mechanism that promotes effective defense without altering baseline immunity.

immunology↗

Neuronal NPR-15 controls the interplay between molecular and behavioral immune responses through the amphid sensory neuron-intestinal axis in C. elegans

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 interaction 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. Our study contributes to a broader understanding of host defense strategies and mechanisms underlining the interaction between molecular and behavioral immune responses.

immunology↗

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

A body of evidence indicates that metazoan immune and aging pathways are largely interconnected, but the mechanisms involved in their homeostatic control remain unclear. In this study, we found that the PITX (paired like homeodomain) transcription factor UNC-30 controls the tradeoff between immunity and longevity from the nervous system in Caenorhabditis elegans. PITX/UNC-30 functional loss enhanced immunity in a GATA/ELT-2- and p38 MAPK/PMK-1-dependent manner and reduced longevity by activating MXD/MDL-1 and the C2H2-type zinc finger transcription factor PQM-1. The immune inhibitory and longevity stimulatory functions of PITX/UNC-30 required the sensory neuron ASG and a neurotransmitter signaling pathway controlled by NPR-1, which is a G protein-coupled receptor related to mammalian neuropeptide Y receptors. Our findings uncovered a suppressive role of GABAergic signaling in the neural control of a biological tradeoff where energy is allocated towards immunity at the expense of longevity.

immunology↗

Shotgun Proteomics of non-depleted and depleted hemolymph of human Schistosomiasis snail vector; Biomphalaria glabrata, revealed vital immune related proteins

BackgroundBiomphalaria glabrata is an important host in the transmission of human schistosomiasis in the Caribbean and South America. There are serious setbacks in the current control measures, hence need to explore alternatives. ObjectiveTo unveil Biomphalaria glabrata hemolymph proteome for possible detailed knowledge of its immunity in host-pathogen relationship. MethodsIn this study we performed a shotgun proteomic and bioinformatic analyses of the non-depleted and depleted [0.5 and 0.75% Trifluoroacetic acid (TFA) depletion] hemolymph of B. glabrata (LE strain). ResultsOur analysis was able to mine a total of 148 proteins from the hemolymph. The highest number of protein (148) was obtained from the 0.5% TFA-depleted sample, followed by 62 proteins from the 0.75% TFA-depleted sample and only 59 from non-depleted hemolymph. ConclusionMost of these proteins are novel and some of them may perform an important role in the immunity of this snail against invading pathogens.

immunology↗