Abstract
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.
Acknowledgements
We thank Michael Shapira (University of California, Berkeley) for sharing bacterial strains, the Caenorhabditis Genetic Center (University of Minnesota) for C. elegans strains, Anton Gartner (UNIST, Korea) for support, and the Yonsei Institute of Space Biosciences (Wonju, S. Korea) for support. We also thank the European and UK Space Agencies for supporting the MME-2 spaceflight mission, ESA astronaut Thomas Pesquet for installing the MME-2 aboard the ISS Columbus Module, JAXA and AES Co., Ltd. for providing the Portable Microgravity Simulator. This work was supported by the National Research Foundation of Korea (NRF) grant number 2021R1A2C101178312 (J.I.L.), NRF grant funded by the Ministry of Science and Technology RS-2024-00409403 (J.I.L.), NRF grant funded by the Ministry of Science and Technology RS-2024-00460066 (H.S.K), the Korean National Institute of Health, award number: RS-2025-02263513 (R.J.M.) and the Asian Office of Aerospace Research and Development, division of the Air Force Office of Scientific Research, award number: FA2386-24-1-4002 (J.I.L.), and was supported (in part) by the Yonsei University Research Fund (Yonsei University Frontier Fellowship for Postdoctoral Researchers) 2024-52-0061 (A.V.A.J.) This manuscript was submitted posthumously and dedicated to Nathaniel "Nate" J. Szewczyk.
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Alcantara, A.V., Indong, R.A., Yoon, Kh. et al. MAPK/PMK-1 innate immune signaling protects the nematode Caenorhabditis elegans from increased intestinal colonization in an animal host-pathogen model in space. npj Microgravity (2026). https://doi.org/10.1038/s41526-026-00603-2
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DOI: https://doi.org/10.1038/s41526-026-00603-2
