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

Emma C Reilly,Kris Lambert-Emo,David J Topham,Steven M Varga

doi:10.1371/journal.pone.0164247

Emma C Reilly, Kris Lambert-Emo + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0164247

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Journal: PloS one	Publication Date: Oct 14, 2016
Citations: 17	License type: CC BY 4.0

Affiliation: University of Rochester Medical Center

Abstract

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.

Highlights

Neutrophil depletion during acute influenza infection of the lung We have previously shown that depletion of neutrophils during acute influenza infection limited CD8+ T cell infiltration on day 7 of infection and delayed viral clearance[35]
No consistent significant differences were observed in the number of NP tetramer+ T cells in the lung (Fig 1C) or Bronchoalveolar lavage (BAL) (Fig 1D) at day 6 post-infection in neutrophil depleted mice compared with controls, which can likely be attributed to variability in the early adaptive response
As we previously described, elimination of neutrophils, and neutrophil derived CXCL12, perturbs this response, and results in lower virus-specific CD8+ T cell numbers, localization distal to the airways compared to controls, and delayed clearance of virus[35]

Summary

Introduction

No consistent significant differences were observed in the number of NP tetramer+ T cells in the lung (Fig 1C) or BAL (Fig 1D) at day 6 post-infection in neutrophil depleted mice compared with controls, which can likely be attributed to variability in the early adaptive response. At day 8 comparable to other reports at similar time points [35,36], significantly lower numbers of NP tetramer+ virus specific CD8+ T cells were found in the lung tissue, but not in the BAL (Fig 1C).

Results

Conclusion