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<p>With the recent rise in the numbers and diversity of astronauts and space travelers, health and prevention of illness in space are of primary importance. Changes in immune function among astronauts during spaceflight have been reported, but gaps remain in understanding how this may translate to increases in an in-flight risk of infection. To understand how immunity and infection are affected by microgravity, we used the nematode <i>Caenorhabditis elegans</i> as an animal host-pathogen model. Worms exposed to either space or simulated microgravity for several days exhibited increased <i>Enterobacter</i> gut colonization compared to normal gravity on Earth. Bacterial susceptibility was more severe in immunocompromised mutants of the <i>pmk-1</i> gene, a conserved p38 MAPK ortholog that regulates innate immunity. RNA sequencing analysis identified several immune effector genes regulated by microgravity through MAPK/PMK-1. Silencing these genes via RNA interference identified specific immune effectors that protect <i>C. elegans</i> against increased <i>Enterobacter</i> gut proliferation, while transgenic expression of one of these effectors prevented increased colonization in immunocompromised <i>C. elegans</i> in microgravity. This study underscores the importance of the conserved MAPK/PMK-1 innate immune pathway in providing protection against possible infection during spaceflight.</p>

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MAPK/PMK-1 innate immune signaling protects the nematode Caenorhabditis elegans from increased intestinal colonization in an animal host-pathogen model in space

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月6日

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  • Alfredo V. Alcantara Jr.,
  • Rocel Amor Indong,
  • Kyoung-hye Yoon,
  • Ban-seok Kim,
  • Toko Hashizume,
  • Akira Higashibata,
  • Atsushi Higashitani,
  • Nathaniel J. Szewczyk,
  • Timothy Etheridge,
  • Colleen S. Deane,
  • Rebecca A. Ellwood,
  • Han Sung Kim,
  • Robert J. Mitchell,
  • Jin I. Lee

摘要

With the recent rise in the numbers and diversity of astronauts and space travelers, health and prevention of illness in space are of primary importance. Changes in immune function among astronauts during spaceflight have been reported, but gaps remain in understanding how this may translate to increases in an in-flight risk of infection. To understand how immunity and infection are affected by microgravity, we used the nematode Caenorhabditis elegans as an animal host-pathogen model. Worms exposed to either space or simulated microgravity for several days exhibited increased Enterobacter gut colonization compared to normal gravity on Earth. Bacterial susceptibility was more severe in immunocompromised mutants of the pmk-1 gene, a conserved p38 MAPK ortholog that regulates innate immunity. RNA sequencing analysis identified several immune effector genes regulated by microgravity through MAPK/PMK-1. Silencing these genes via RNA interference identified specific immune effectors that protect C. elegans against increased Enterobacter gut proliferation, while transgenic expression of one of these effectors prevented increased colonization in immunocompromised C. elegans in microgravity. This study underscores the importance of the conserved MAPK/PMK-1 innate immune pathway in providing protection against possible infection during spaceflight.