Journal Article

Neutrophil trails guide influenza-specific CD8+T cells in the airways

Lambert-Emo, Kris, Lim, Kihong, Hyun, Young-Min, Capece, Tara, Bae, Seyeon, Kim, Minsoo, Miller, Richard, Topham, David J.

2015

Overview

T cells constantly circulate throughout the body until an invading pathogen calls them into action. Microbes often cause localized infections, so how do T cells know where to go? Lim et al. explore this question in a mouse model of influenza infection and find that immune cells called neutrophils help guide the way (see the Perspective by Kiermaier and Sixt). Upon infection, neutrophils quickly traffic to the trachea. There, they lay down “tracks” enriched in proteins called chemokines, especially the chemokine CXCL12, which guide CD8 + T cells to the infected organ. Mice whose neutrophils could not lay down such tracks exhibited defects in CD8 + T cell recruitment and viral clearance. Science , this issue 10.1126/science.aaa4352 ; see also p. 1055 Trails of chemokines left behind by neutrophils guide T cells to sites of viral infection. [Also see Perspective by Kiermaier and Sixt ] 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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / CD8-Positive T-Lymphocytes - immunology / Chemokine CXCL12 - immunology / Chemokine CXCL12 - pharmacology / Chemotaxis - immunology / Depletion / Distribution patterns / Effectors / Enrichment / Heterocyclic Compounds - pharmacology / Immune response / Influenza A virus - immunology / Lung - immunology / Lung - virology / Male / Matrix Metalloproteinase 2 - immunology / Matrix Metalloproteinase 9 - immunology / Mice / Mice, Inbred C57BL / Migration / Neutropenia - immunology / Neutrophils - immunology / Neutrophils - virology / Orthomyxoviridae Infections - immunology / Position (location) / Recruitment / RESEARCH ARTICLE SUMMARY / Respiratory tract / Tissues / Trachea / Trachea - immunology / Trachea - virology / Tracks (paths) / Trails