MSGID: 1:317/3 64080f78   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
   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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