<p>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.</p>

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

  • Daphne Kolland,
  • Miriam Kuhlmann,
  • Gustavo P. de Almeida,
  • Amelie Köhler,
  • Anela Arifovic,
  • Alexandra von Strempel,
  • Mohsen Pourjam,
  • Silvia Bolsega,
  • Christine Wurmser,
  • Katja Steiger,
  • Marijana Basic,
  • Klaus Neuhaus,
  • Carsten B. Schmidt-Weber,
  • Bärbel Stecher,
  • Dietmar Zehn,
  • Caspar Ohnmacht

摘要

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.