Worm cells sense metabolism changes to stimulate their defense against pathogens

Microbial infections form part of the wider repercussions of the COVID-19 pandemic, and researchers are focusing more on such infections and how life forms fight against attacks by pathogens.

Worm cells sense metabolism changes to stimulate their defense against pathogens
Worms with alterations in purine metabolism are shown triggering an immune response without pathogen infection. The immune response is revealed through green fluorescence in mutant worm intestines (middle and right) and not in control worms (left). Image Credit: University of California San Diego.

A new study by researchers from the University of California San Diego throws new light on the complex dynamics that form part of how organisms sense the occurrence of an infection.

Eillen Tecle, a UC San Diego Assistant Project Scientist in Professor Emily Troemel’s laboratory (Division of Biological Sciences), headed the study that paid attention to how cells that are not part of the regular immune system respond to infections upon attack by pathogens.

Researchers have performed wide-scale research on what are called “professional” immune cells that are defensive specialists. Not much is known about how “non-professional” cells address such threats.

Tecle, Troemel, and their collaborators from Pennsylvania State University focused their study on roundworms (Caenorhabditis elegans), animals that lack dedicated immune cells, to help unravel the details of such dynamics.

As explained in the PLOS Pathogens journal, the team performed experiments with roundworms under attack by microsporidia and viruses—natural pathogens of worms and humans. The findings show that roundworms might sense variations in their metabolism to unleash protective defenses, even if they do not directly sense the pathogen incursion.

As part of the study, the researchers investigated how hosts may respond when pathogens like microsporidia and viruses steal crucial compounds from C. elegans cells called nucleotides. Pathogens such as these must pilfer such components from their hosts to survive.

The findings of the study focused on biological pathways associated with the disintegration of chemical compounds called purine nucleotides. This purine metabolism pathway is crucial for the ability of the cells to sense modifications as a means to induce an immune response.

We hypothesize that the host has ways to surveil what’s going on inside of its cells in an active process. Our results suggest that the host has developed ways to sense the theft of purine metabolites. It seems that when these key cellular building blocks are stolen by the pathogen, the host senses this theft to mount an immune response to the pathogen.”

Eillen Tecle, Assistant Project Scientist, University of California San Diego

This study could help unravel why purine-related compound mutations have been identified to be the base for several human diseases, such as adenosine deaminase deficiency, which affects the immune system, and Lesch-Nyhan syndrome, which causes behavioral and neurological abnormalities.

Although these mutations lead to several disorders in humans, they may still persist in the human population to offer some protection against infections, for instance, during viral pandemics.

Particularly in the context of the COVID-19 pandemic, it’s so important that we continue to study these questions of immunity in lots of different systems to build new tools so that we can learn how to prevent and treat infections.”

Emily Troemel, Professor, Division of Biological Sciences, University of California San Diego

Source:
Journal reference:

Tecle, E., et al. (2021) The purine nucleoside phosphorylase pnp-1 regulates epithelial cell resistance to infection in C. elegans. PLOS Pathogens. doi.org/10.1371/journal.ppat.1009350.

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