A specific microbial consortium enhances Th1 immunity, improves LCMV viral clearance but aggravates LCMV disease pathology in mice

Daphne Kolland, Miriam Kuhlmann, Gustavo P. Almeida, Amelie Köhler, Anela Arifovic, Alexandra Strempel, Mohsen Pourjam, Silvia Bolsega, Christine Wurmser, Katja Steiger, Marijana Basic, Klaus Neuhaus, Carsten B. Schmidt-Weber, Bärbel Stecher, Dietmar Zehn () and Caspar Ohnmacht ()
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Daphne Kolland: Technical University and Helmholtz Center
Miriam Kuhlmann: Technical University of Munich
Gustavo P. Almeida: Technical University of Munich
Amelie Köhler: Technical University and Helmholtz Center
Anela Arifovic: Technical University and Helmholtz Center
Alexandra Strempel: LMU
Mohsen Pourjam: Technical University of Munich
Silvia Bolsega: Hannover Medical School
Christine Wurmser: Technical University of Munich
Katja Steiger: Technical University Munich
Marijana Basic: Hannover Medical School
Klaus Neuhaus: Technical University of Munich
Carsten B. Schmidt-Weber: Technical University and Helmholtz Center
Bärbel Stecher: LMU
Dietmar Zehn: Technical University of Munich
Caspar Ohnmacht: Technical University and Helmholtz Center

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Anti-viral immunity can vary tremendously from individual to individual but mechanistic understanding is still scarce. Here, we show that a defined, low complex bacterial community (OMM12) but not the general absence of microbes in germ-free mice leads to a more potent immune response compared to the microbiome of specific-pathogen-free (SPF) mice after a systemic viral infection with LCMV Clone-13. Consequently, gnotobiotic mice colonized with OMM12 have more severe LCMV-induced disease pathology but also enhance viral clearance in the intestinal tract. Mechanistically, single-cell RNA sequencing analysis of adoptively transferred virus-specific T helper cells and endogenous T helper cells in the intestinal tract reveal a stronger pro-inflammatory Th1 profile and a more vigorous expansion in OMM12 than SPF mice. Altogether, our work highlights the causative function of the intestinal microbiome for shaping adaptive anti-viral immunity with implications for vaccination strategies and anti-cancer treatment regimens.

Date: 2025
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DOI: 10.1038/s41467-025-59073-x

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