Neutrophil trails guide influenza-specific CD8⁺ T cells in the airways.
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.
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
Kihong
K
Lim
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
Young-Min
YM
Hyun
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
Kris
K
Lambert-Emo
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
Tara
T
Capece
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
Seyeon
S
Bae
Department of Pharmacology, Northwestern University, Chicago, IL, USA.
Richard
R
Miller
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
David J
DJ
Topham
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA. minsoo_kim@urmc.rochester.edu.
Minsoo
M
Kim
D000818:Animals; D001596:Benzylamines; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054377:Chemokine CXCL12 / Q000276:immunology* / Q000494:pharmacology; D002633:Chemotaxis / Q000276:immunology*; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000494:pharmacology; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009503:Neutropenia / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D014132:Trachea / Q000276:immunology* / Q000821:virology
D001596:Benzylamines; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C088327:plerixafor