Immunity system complexity: detecting danger in C elegans (Introduction)

by David Turell , Tuesday, November 12, 2024, 19:05 (143 days ago) @ David Turell

Molecular defenses:

https://www.the-scientist.com/worms-nose-for-danger-helps-ward-off-pathogens-72309

"Just like humans, Caenorhabditis elegans worms encounter gut-attacking bacterial pathogens through their diet. To thrive in their new hosts, bacteria seek out iron. To protect their iron supplies, which are stored in mitochondria, the worms activate a defense tactic. How the worms detect these environmental threats and trigger a mitochondrial response intrigued scientists, including Andrew Dillin, a molecular and cell biologist at the University of California, Berkeley.

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"Dillin and his team showed that C. elegans worms’ sense of smell coordinates a mitochondrial response, particularly in intestinal cells, to resist bacterial infection.1 The researchers speculate that this process is conserved in mammals for pathogen detection and immune regulation.

"The researchers focused their investigation on a pair of olfactory neurons called amphid wing "C" (AWC), which serve as a scent detection system by activating in the absence of odor and turning off when odors are present. Researchers previously found that ablating these neurons boosted pathogen resistance and improved worm survival.2 However, it was unclear how this might be connected to the mitochondrial stress response.

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"Not only did these worms show resistance to infection, but they also exhibited an increase in activity of a transcription factor that typically shows up during the mitochondrial unfolded protein response (UPRMT), a process triggered when mitochondria are overwhelmed with an onslaught of misfolded proteins. This led to changes indicative of protective efforts: reduced oxidative phosphorylation, oxygen consumption rates, and mitochondrial DNA (mtDNA) levels.

"Under the microscope, they found that the pathogen triggered mitochondrial responses throughout the bodies of AWC-silenced worms. These worms had a reduced intensity of stain, indicating fewer mitochondria, which correlated with lower activity and mtDNA levels. These findings suggest that smelling a pathogen prepares the worm’s gut against infection.

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"The researchers tested whether loss of tryptophan hydrolase 1, the gene required for serotonin synthesis, was required for AWC-mediated UPRMT induction. The absence of serotonin signaling inhibited the mitochondrial stress response, but exogenous serotonin supplementation activated UPRMT, showing that mitochondrial changes rely on serotonin signaling.

"Dillin wondered whether the loss of AWC affected mitophagy, another maintenance pathway that removes damaged or excess mitochondria, and if the observed reduction in oxygen consumption and mtDNA was a consequence of mitochondrial clearance. Mutant worms lacking a key mitophagy gene were more sensitive to P. aeruginosa infection. When Dillin and his team delved into the mechanisms underlying this effect, they found that the mitophagy gene is required for the reduction in oxygen consumption and mtDNA observed in AWC-ablated worms.

“'And [this olfactory response] actually does even more than protect mitochondria. It [caused mitophagy], splitting the mitochondria up into smaller units, so there's less opportunities for the pathogen and it can't find all the mitochondria,” said Dillin. Although mitophagy seems to be an anticipatory strategy to resist pathogenic insult, Dillin noted that there is still much to learn about this process."

Comment: this is a clear example of an automatic protein trigger for response to a specific danger. No thought involved.