Lim Kihong, Hyun Young-Min, Lambert-Emo Kris, Capece Tara, Bae Seyeon, Miller Richard, Topham David J, Kim Minsoo
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
Department of Pharmacology, Northwestern University, Chicago, IL, USA.
Science. 2015 Sep 4;349(6252):aaa4352. doi: 10.1126/science.aaa4352.
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.
在病毒感染期间，趋化因子引导活化的效应T细胞前往感染部位。然而，负责产生这些趋化因子的细胞以及此类趋化因子如何招募T细胞尚不清楚。在此，我们表明，中性粒细胞早期募集到感染流感的气管中对于小鼠CD8(+) T细胞介导的免疫保护至关重要。我们观察到，迁移的中性粒细胞会留下富含趋化因子CXCL12的持久痕迹。对粒细胞特异性CXCL12条件性缺失小鼠和CXCR4拮抗剂进行的实验表明，源自中性粒细胞痕迹的CXCL12对于病毒特异性CD8(+) T细胞的募集和效应功能至关重要。总体而言，这些结果表明，中性粒细胞会沉积持久的、含有趋化因子的痕迹，这可能为CD8(+) T细胞在感染流感的组织中高效迁移和定位提供趋化和触觉线索。
