After airways become infected with influenza, the body mounts both an early and late immune response to contain the infection and kill virally infected cells. This carefully orchestrated response relies on communication between two arms of the immune system: the early response is mediated by cells of the innate immune system, including neutrophils, which are activated by conserved motifs (patterned components) of the virus; the adaptive immune response arises later and consists of T and B cells that react to the virus itself.

Animal models are essential for determining the kinetics of this response, as the first immune responders use molecular mechanisms to recruit other cells to the infection from anatomically distinct sites. Minsoo Kim and colleagues from the University of Rochester examined the interaction between neutrophils and T cells (Science 349, aaa4352; 2015). In C57BL/6 mice infected with HKx31 influenza virus neutrophils are rapidly recruited to the lungs, peaking at day 4, and are followed by a wave of CD8+ T cells from days 6 to 8. If neutrophils are depleted, fewer CD8+ T cells accumulate in the lungs after infection and viral clearance is impaired.

Soluble factors called chemokines guide immune cells to particular anatomical sites, and during in vivo viral infection, neutrophils were a major source of the chemokine CXCL12. Among infected mice whose neutrophils could not produce CXCL12, T cells were recruited the lung much later. Furthermore, after neutrophils were placed on coverslips in vitro, allowed to migrate, then washed away, CD8+ T cells that were added to the coverslips were also found to migrate. Migrating neutrophils appear to leave trails of chemokines behind them. As they migrate, the neutrophils extend processes and deposit CXCL12 with components of their membrane.

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Neutrophils in infected mice exhibited similar crawling movement in the lung, extending processes as they migrated toward the site of infection and leaving behind CXCL12 in the trachea. These trails of chemokines persist in the airways during infection. Since chemokines are small and readily diffusible, this establishes a depot of sorts that signals T cells to migrate into the tissue and home in on the site of infection. Using mice as in vivo models of infection, Kim's team has now teased apart important characteristics of the tissue microenvironment to show how signals released from innate immune cells are retained in the inflammatory environment of the infected lung and recruit adaptive immune cells.