• Immune response to parasitic worms

    From ScienceDaily@1:317/3 to All on Wed Apr 13 22:30:44 2022
    Immune response to parasitic worms

    Date:
    April 13, 2022
    Source:
    University of Minnesota Medical School
    Summary:
    New research looked at if exposure to pathogens, in particular
    helminths, can stimulate the immune system and reduce predisposition
    for inflammatory bowel disease.



    FULL STORY ========================================================================== According to the World Health Organization, more than 1 billion people
    are infected with parasitic helminths worldwide, but the prevention
    and treatment of helminth infection remain challenging. Research led
    by the University of Minnesota Medical School looked at if exposure to pathogens, in particular helminths, can stimulate the immune system and
    reduce predisposition for inflammatory bowel disease (IBD).


    ==========================================================================
    "We know that intestinal epithelial cells are first responders to
    invading gut parasites, through secreting cytokines that alarms and
    guides immune cells for worm expulsion," said Hai-Bin Ruan, PhD, an
    assistant professor at the U of M Medical School. "We found that a unique glycosylation within epithelial cells, termed as O-GlcNAcylation, can be activated during helminth infections to orchestrate alarmin secretion
    and facilitate anti-helminth immune responses." There is a growing
    interest in the use of helminth therapy for IBD, but clinical data have
    been inconclusive and the direct use of helminths has obvious safety and efficacy concerns. A greater understanding of host defense mechanisms
    against helminths is essential for the development of effective and safe treatments for intestinal infections and inflammation.

    Published in Immunity, the study found that:
    * O-GlcNAc glycosylation modifies and activates the STAT6 protein,
    a master
    transcriptional regulator of the type 2 anti-helminth immunity;
    * STAT6 O-GlcNAcylation in epithelial cells alarms immune cells by
    instructing intestinal stem cells to make more "tuft cells" and
    epithelial cells to form membrane pores (composed of GSDMC proteins)
    to meditate alarmin cytokines; and,
    * GSDMC is induced and activated in IBD preclinical models.

    "Our study established a novel post translational regulatory switch
    to turn on epithelial alarmin responses to fight helminth infections,"
    said Ruan.

    The research team plans to investigate how O-GlcNAc glycosylation is
    activated by helminth infections and how GSDMC protein is cleaved to
    form active membrane pores in human IBD in the future.

    The study was funded by the National Institutes of Health (NIH/NIAID)
    and includes collaborators from Nanjing University, Xinxiang University,
    and University of Washington.


    ========================================================================== Story Source: Materials provided by
    University_of_Minnesota_Medical_School. Original written by Kat
    Dodge. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Ming Zhao, Kaiqun Ren, Xiwen Xiong, Yue Xin, Yujie Zou, Jason
    C. Maynard,
    Angela Kim, Alexander P. Battist, Navya Koneripalli, Yusu Wang,
    Qianyue Chen, Ruyue Xin, Chenyan Yang, Rong Huang, Jiahui Yu,
    Zan Huang, Zengdi Zhang, Haiguang Wang, Daoyuan Wang, Yihui Xiao,
    Oscar C. Salgado, Nicholas N. Jarjour, Kristin A. Hogquist, Xavier
    S. Revelo, Alma L.

    Burlingame, Xiang Gao, Jakob von Moltke, Zhaoyu Lin, Hai-Bin Ruan.

    Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth
    alarmin response dependent on tuft cell hyperplasia and Gasdermin
    C. Immunity, 2022; 55 (4): 623 DOI: 10.1016/j.immuni.2022.03.009 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220413131133.htm

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