Influenza infection is confined to the lung epithelium and its control depends, among other factors, upon an effective local T lymphocyte response. Protective immunity is correlated with influenza-specific memory T lymphocytes that persist in the airways for extended periods of time. Thus, T lymphocyte recruitment is central for protection and memory to influenza. Control of lymphocyte migration is a complex process mediated by several mechanisms including selectins, integrins and chemokines, and it is orchestrated by early inflammatory signals. However, the early innate cytokines that mediate the recruitment of T lymphocytes during primary influenza infection to the site of infection are not well characterized. The overall goal of this project is to identify the molecular mechanisms that dictate CD8 T lymphocyte recruitment at the onset of infection with influenza virus. First, we will identify the mechanisms that regulate CD8 T cell recruitment and function during influenza infection. Second, we will build on this information to determine how this process is regulated in the lung and how it impacts protection against influenza infection. To develop more effective influenza treatments and vaccines, it is essential that we have a better understanding of the mechanisms that regulate cell-mediated immunity in the lung during influenza infection.
|McNally, Beth; Ye, Fang; Willette, Meredith et al. (2013) Local blockade of epithelial PDL-1 in the airways enhances T cell function and viral clearance during influenza virus infection. J Virol 87:12916-24|
|Ioannidis, Ioannis; Ye, Fang; McNally, Beth et al. (2013) Toll-like receptor expression and induction of type I and type III interferons in primary airway epithelial cells. J Virol 87:3261-70|
|McNally, Beth; Willette, Meredith; Ye, Fang et al. (2012) Intranasal administration of dsRNA analog poly(I:C) induces interferon-? receptor-dependent accumulation of antigen experienced T cells in the airways. PLoS One 7:e51351|
|Ye, Fang; Turner, Joanne; Flano, Emilio (2012) Contribution of pulmonary KLRG1(high) and KLRG1(low) CD8 T cells to effector and memory responses during influenza virus infection. J Immunol 189:5206-11|
|Ioannidis, Ioannis; McNally, Beth; Willette, Meredith et al. (2012) Plasticity and virus specificity of the airway epithelial cell immune response during respiratory virus infection. J Virol 86:5422-36|