Lara Labarta-Bajo, Steven P. Nilsen, Gregory Humphrey, Tara Schwartz, Karenina Sanders, Austin Swafford, Rob Knight, Jerrold R. Turner, and Elina I. Zuñiga
Intestinal barrier leakage constitutes a potential therapeutic target for many inflammatory diseases and represents a disease progression marker during chronic viral infections. However, the causes of altered gut barrier remain mostly unknown. Using murine infection with lymphocytic choriomeningitis virus, we demonstrate that, in contrast to an acute viral strain, a persistent viral isolate leads to long-term viral replication in hematopoietic and mesenchymal cells, but not epithelial cells (IECs), in the intestine. Viral persistence drove sustained intestinal epithelial barrier leakage, which was characterized by increased paracellular flux of small molecules and was associated with enhanced colitis susceptibility. Type I IFN signaling caused tight junction dysregulation in IECs, promoted gut microbiome shifts and enhanced intestinal CD8 T cell responses. Notably, both type I IFN receptor blockade and CD8 T cell depletion prevented infection-induced barrier leakage. Our study demonstrates that infection with a virus that persistently replicates in the intestinal mucosa increases epithelial barrier permeability and reveals type I IFNs and CD8 T cells as causative factors of intestinal leakage during chronic infections.
Labarta-Bajo, L., Nilsen, S.P., Humphrey. G., et al. Type I IFNs and CD8 T cells increase intestinal barrier permeability after chronic viral infection. J Exp Med (2020) 217 (12): e20192276. https://doi.org/10.1084/jem.20192276.
The following Bio X Cell in vivo monoclonal antibodies were featured in the publication:
- anti-mouse CD8α (Clone 53-6.7, Bio X Cell catalog no. BP0004-1; BE0004-1)
- anti-mouse CD4 (Clone GK1.5, Bio X Cell catalog no. BP0003-1; BE0003-1)
- rat IgG2a isotype control (Clone 2A3, Bio X Cell catalog no. BP0089; BE0089)
- anti-mouse IFNAR-1 (Clone MAR1-5A3, Bio X Cell catalog no. BP0241; BP0241)
- mouse IgG1 isotype control, unknown specificity (Clone MOPC-21, Bio X Cell catalog no. BP0083; BE0083)