A specific microbial consortium enhances Th1 immunity, improves LCMV viral clearance but aggravates LCMV disease pathology in mice
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 (OMM<sup>12</sup>) 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 OMM<sup>12</sup> 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 OMM<sup>12</sup> 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.
Authors
- Katja Steiger (ORCID: https://orcid.org/0000-0002-7269-5433)
- Caspar Ohnmacht (ORCID: https://orcid.org/0000-0002-6887-8819)
- Dietmar Zehn (ORCID: https://orcid.org/0000-0003-1393-8527)
- Marijana Basic (ORCID: https://orcid.org/0000-0002-1995-618X)
- Alexandra von Strempel (ORCID: https://orcid.org/0000-0003-0173-3022)
- Anela Arifovic
- Christine Wurmser (ORCID: https://orcid.org/0000-0003-0649-6206)
- Mohsen Pourjam (ORCID: https://orcid.org/0000-0003-3904-8100)
- Klaus Neuhaus (ORCID: https://orcid.org/0000-0002-6020-2814)
- Miriam Kuhlmann (ORCID: https://orcid.org/0000-0001-7431-9637)
- Gustavo P. de Almeida (ORCID: https://orcid.org/0000-0002-2424-9818)
- Daphne Kolland
- Bärbel Stecher (ORCID: https://orcid.org/0000-0002-7445-5193)
- Carsten B. Schmidt‐Weber (ORCID: https://orcid.org/0000-0002-3203-8084)
- Silvia Bolsega
- Amelie Köhler (ORCID: https://orcid.org/0009-0000-1389-614X)
Institutions
- Helmholtz Zentrum München (DE)
- Medizinische Hochschule Hannover (DE)
- German Center for Infection Research (DE)
- German Center for Lung Research (DE)
- Institute of Medical Microbiology and Hygiene (DE)
- Leibniz-Institute for Food Systems Biology at the Technical University of Munich (DE)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1038/s41467-025-59073-x
- Citations
- 2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Deutsche Forschungsgemeinschaft