Kihong Lim1,*, Young-Min Hyun1,*, Kris Lambert-Emo1, Tara Capece1, Seyeon Bae1, Richard Miller2, David J. Topham1, Minsoo Kim1,†
1Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
2Department of Pharmacology, Northwestern University, Chicago, IL, USA.
†Corresponding author
* These authors contributed equally to this work.
Abstract
During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells are unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8† T cell-mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditionally depleted mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8† T cell recruitment and effector functions. Collectively, these results suggest that neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8† T cell migration and localization in influenza-infected tissues.