The Effects of Acute Neutrophil Depletion on Resolution of Acute Influenza Infection, Establishment of Tissue Resident Memory (T_RM), and Heterosubtypic Immunity

After disease resolution, a small subset of influenza specific CD8+ T cells can remain in the airways of the lung as a tissue resident memory population (TRM). These cells are critical for protection from subsequent infections with heterosubtypic influenza viruses. Although it is well established that expression of the collagen IV binding integrin alpha 1 is necessary for the retention and maintenance of TRM cells, other requirements allowing them to localize to the airways and persist are less well understood. We recently demonstrated that inhibition of neutrophils or neutrophil derived chemokine CXCL12 during acute influenza virus infection reduces the effector T cell response and affects the ability of these cells to localize to the airways. We therefore sought to determine whether the defects that occur in the absence of neutrophils would persist throughout resolution of the disease and impact the development of the TRM population. Interestingly, the early alterations in the CD8+ T cell response recover by two weeks post-infection, and mice form a protective population of TRM cells. Overall, these observations show that acute neutrophil depletion results in a delay in the effector CD8+ T cell response, but does not adversely impact the development of TRM.流感康复后，少量流感特异性CD8+ T细胞可作为组织驻留记忆细胞群（tissue resident memory population, TRM）留存于肺气道内。这类细胞对于抵御后续异型流感病毒感染具有关键保护作用。尽管已有研究证实，结合IV型胶原的整合素α1（integrin alpha 1）的表达是TRM细胞留存与维持的必要条件，但关于TRM细胞定位于气道并持续存活的其他必要条件，目前仍尚未完全阐明。我们此前的研究发现，在急性流感病毒感染期间抑制中性粒细胞或中性粒细胞衍生的趋化因子CXCL12，会降低效应T细胞应答水平，并影响此类细胞定位于气道的能力。因此，本研究旨在明确：中性粒细胞缺失所引发的细胞缺陷是否会在疾病康复全程中持续存在，并影响TRM细胞群的形成。值得注意的是，感染两周后，CD8+ T细胞应答的早期改变已完全恢复，小鼠可形成具有保护功能的TRM细胞群。综上，本研究结果表明：急性中性粒细胞耗竭会导致效应CD8+ T细胞应答延迟，但并不会对TRM细胞的形成产生不利影响。