Author:
Kuhlmann Miriam,Del Carmen Kolland Daphne,de Almeida Gustavo Pereira,Hoffmann Christian,von Hoesslin Madlaina,Berner Jacqueline,Wurmser Christine,Ohnmacht Caspar,Zehn Dietmar
Abstract
ABSTRACTProlonged antigen exposure in chronic viral infections reduces the effector capacity of cytotoxic T cells - a phenomenon known as T cell exhaustion. High viral titer, strong TCR stimulation, and high antigen concentrations associated with strong inflammatory signals are known factors that promote the development of T cell exhaustion. A largely unexplored factor has been the influence of the microbiome on the development of T cell exhaustion. We report that T cell exhaustion progresses independently of the presence or absence of a bacterial 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 stark contrast to the phenotypic similarities, the absence of the microbiome delayed the partial viral control typically seen in chronic LCMV infections. Thus, our study demonstrates that the microbiome is dispensable for the induction of T cell exhaustion but critical for effector T cell function in chronic LCMV infections.
Publisher
Cold Spring Harbor Laboratory