Absence of microbiome in chronic infections impairs viral control without affecting CD8 T cell function
Kuhlmann, M.; Kolland, D. D. C.; Almeida, G. P. d.; Hoffmann, C.; von Hoesslin, M.; Berner, J.; Wurmser, C.; Ohnmacht, C.; Zehn, D.
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Prolonged antigen exposure in chronic viral infections reduces the effector capacity of cytotoxic T cells - a phenomenon known as T cell exhaustion. Development of T cell exhaustion is driven by high viral titers, strong TCR stimulation, and high antigen concentrations associated with strong inflammatory signals. A largely unexplored factor has been the influence of the microbiome in these processes. Here, we report that T cell exhaustion progresses independently of the presence or absence of a microbiome in chronic lymphocytic choriomeningitis virus (LCMV) infections. Virus-specific CD8 T cells in germ-free mice showed high expression of the inhibitory receptor PD-1 and decreased cytokine production. Moreover, their global gene expression patterns, as determined by single-cell sequencing, were similar to those of cells in specific pathogen-free mice. In line with this, we observed similar pathogen loads with and without a microbiome. Thus, our study demonstrates that the microbiome is dispensable for the induction of T cell exhaustion and for the limited virus control seen in chronic LCMV infections.
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