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Pulmonary monocytes interact with effector T cells in the lung tissue to drive TRM differentiation following viral infection

tetano

Editor, Senior Moderator
Mucosal Immunol. 2019 Nov 13. doi: 10.1038/s41385-019-0224-7. [Epub ahead of print] [h=1]Pulmonary monocytes interact with effector T cells in the lung tissue to drive T[SUB]RM[/SUB] differentiation following viral infection.[/h]
Dunbar PR[SUP]1[/SUP], Cartwright EK[SUP]1[/SUP], Wein AN[SUP]1[/SUP], Tsukamoto T[SUP]2[/SUP], Tiger Li ZR[SUP]1[/SUP], Kumar N[SUP]1[/SUP], Uddb?ck IE[SUP]3[/SUP], Hayward SL[SUP]1[/SUP], Ueha S[SUP]4[/SUP], Takamura S[SUP]2[/SUP], Kohlmeier JE[SUP]5,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA. 2 Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka, 589-8511, Japan. 3 Department of Microbiology and Immunology, University of Copenhagen, 1165, Copenhagen, Denmark. 4 Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8654, Japan. 5 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA. jkohlmeier@emory.edu. 6 Emory-UGA Center of Excellence for Influenza Research and Surveillance, Atlanta, GA, USA. jkohlmeier@emory.edu.

[h=3]Abstract[/h] Lung resident memory CD8 T cells (T[SUB]RM[/SUB]) are critical for protection against respiratory viruses, but the cellular interactions required for their development are poorly understood. Herein we describe the necessity of classical monocytes for the establishment of lung T[SUB]RM[/SUB] following influenza infection. We find that, during the initial appearance of lung T[SUB]RM[/SUB], monocytes and dendritic cells are the most numerous influenza antigen-bearing APCs in the lung. Surprisingly, depletion of DCs after initial T cell priming did not impact lung T[SUB]RM[/SUB] development or maintenance. In contrast, a monocyte deficient pulmonary environment in CCR2[SUP]-/-[/SUP] mice results in significantly less lung T[SUB]RM[/SUB] following influenza infection, despite no defect in the antiviral effector response or in the peripheral memory pool. Imaging shows direct interaction of antigen-specific T cells with antigen-bearing monocytes in the lung, and pulmonary classical monocytes from the lungs of influenza infected mice are sufficient to drive differentiation of T cells in vitro. These data describe a novel role for pulmonary monocytes in mediating lung T[SUB]RM[/SUB] development through direct interaction with T cells in the lung.


PMID: 31723250 DOI: 10.1038/s41385-019-0224-7
 
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