elegans
A nuclear hormone receptor intercepts pathogen-derived signals of growth
and virulence, revealing an evolutionarily ancient strategy of immune sensing


Date:
March 7, 2023
Source:
UMass Chan Medical School
Summary:
Researchers describe a new manner of detecting microbial infection
that intercepts pathogen-derived signals of growth to assess the
relative threat of virulent bacteria. A nuclear hormone receptor
in the nematode C. elegans senses a toxic metabolite produced by
the bacterial pathogen Pseudomonas aeruginosa to activate innate
immunity. These data reveal an ancient strategy that informs the
origins of pathogen detection and may be among the most primordial
forms of immune sensing in animals.


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FULL STORY ==========================================================================
A study published in Immunity by physician-scientist Read Pukkila-Worley,
MD, and MD/PhD students Nicholas D. Peterson and Samantha Y. Tse
describes a new manner of detecting microbial infection that intercepts pathogen-derived signals of growth to assess the relative threat of
virulent bacteria. A nuclear hormone receptor in the nematode C. elegans
senses a toxic metabolite produced by the bacterial pathogen Pseudomonas aeruginosato activate innate immunity.

These data reveal an ancient strategy that informs the origins of pathogen detection and may be among the most primordial forms of immune sensing
in animals.


==========================================================================
"Our research adds to our understanding of how hosts differentiate
between beneficial and harmful bacteria, which teaches us something
important about how our immune systems evolved," said Dr. Pukkila-Worley, associate professor of medicine.

Distinguishing potentially harmful pathogens from benign microorganisms
is one of the primary functions of the innate immune system in all
animals. This is particularly important for nematodes, such as C. elegans
--the transparent microscopic worm often used as a model organism to study genetics and gene function -- that consume bacteria as their food source.

Working with Pseudomonas aeruginosa,a bacteria that commonly infects
immune- compromised patients in the hospital and is increasingly resistant
to standard antibiotic treatments, Pukkila-Worley and colleagues performed
a series of genetic screens with mutant bacteria, one-by-one, to see if
any impacted the innate immune system response inC. elegans.

They found that bacteria that cannot produce a specific phenazine
metabolite were able to avoid detection by the innate immune system,
suggesting that the bacterial phenazine metabolite was sensed to activate innate immunity.

"This result was intriguing because P. aeruginosause phenazines for growth
and virulence. Thus, the innate immune system can intercept signals
produced by bacteria in order to identify bacteria that have grown to
dangerous levels and are poised to cause disease," said Pukkila-Worley.

Researchers in the Pukkila-Worley lab designed a second experiment
to identify the sensor in the host that detects these phenazine
metabolites. They discovered that a specialized type of transcription
factor, a nuclear hormone receptor, binds the phenazine metabolite and
directly activates anti-pathogen defenses.

"One of the striking things about our results is that C. elegans senses
this bacterial metabolite to detect an individual bacterial pathogen in a remarkably specific manner from among its bacterial food,"said Peterson,
an MD/PhD student in the Pukkila-Worley lab.

In humans, pattern-recognition systems in the intestine involving
Toll-like receptors scan the physical structure of different bacteria
to sense the presence of infectious microorganisms. Nematodes lost pattern-recognition receptors in evolution. Pukkila-Worley and colleagues
show that nematodes use nuclear hormone receptors to detect specific pathogen-derived metabolites to activate innate immunity, which represents
a new type of pattern-recognition.

Since C. eleganshave 274 nuclear hormone receptors, it's possible that the nematode genome contains dozens of these metabolite recognition systems.

Nuclear hormone receptors are also found in most animals, including
humans, suggesting that similar metabolite detection systems might exist
in other organisms.

"It's remarkable that C. elegansevolved mechanisms to differentiate
good and bad bacteria even without canonical receptors for pathogen
detection. This further supports the importance of understanding how
our immune system evolved over time to deepen our understanding of host-microbiome interactions," said Tse, an MD/PhD student in the Pukkila-Worley lab.

* RELATED_TOPICS
o Health_&_Medicine
# Immune_System # Foodborne_Illness # Infectious_Diseases
# Lymphoma
o Plants_&_Animals
# Bacteria # Microbes_and_More # Microbiology #
Biotechnology_and_Bioengineering
* RELATED_TERMS
o Pathogen o Growth_hormone_treatment o
Growth_hormone_deficiency o Growth_hormone o Natural_killer_cell
o Encephalitis o Toxic_shock_syndrome o Pituitary_gland

========================================================================== Story Source: Materials provided by UMass_Chan_Medical_School. Original
written by Jim Fessenden. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Nicholas D. Peterson, Samantha Y. Tse, Qiuyu Judy Huang,
Khursheed A.

Wani, Celia A. Schiffer, Read Pukkila-Worley. Non-canonical pattern
recognition of a pathogen-derived metabolite by a nuclear hormone
receptor identifies virulent bacteria in C. elegans. Immunity,
2023; DOI: 10.1016/j.immuni.2023.01.027 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/03/230307144352.htm

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