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

Lung resident memory CD8 T cells (TRM) 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 TRM following influenza infection....

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Bibliographic Details
Published in:Mucosal immunology Vol. 13; no. 1; pp. 161 - 171
Main Authors: Dunbar, Paul R., Cartwright, Emily K., Wein, Alexander N., Tsukamoto, Tetsuo, Tiger Li, Zheng-Rong, Kumar, Nivedha, Uddbäck, Ida E., Hayward, Sarah L., Ueha, Satoshi, Takamura, Shiki, Kohlmeier, Jacob E.
Format: Journal Article
Language:English
Published: New York Elsevier Inc 01.01.2020
Nature Publishing Group US
Elsevier Limited
Subjects:
Allergology
Antibodies
Antigen-presenting cells
Antigens
Antiviral drugs
Biomedical and Life Sciences
Biomedicine
CCR2 protein
CD8 antigen
Cell differentiation
Dendritic cells
Effector cells
Gastroenterology
Immunological memory
Immunology
Infections
Influenza
Lungs
Lymphocytes
Lymphocytes T
Memory cells
Monocyte chemoattractant protein 1
Monocytes
ISSN:1933-0219, 1935-3456, 1935-3456
Online Access:Get full text
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Summary:Lung resident memory CD8 T cells (TRM) 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 TRM following influenza infection. We find that, during the initial appearance of lung TRM, 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 TRM development or maintenance. In contrast, a monocyte deficient pulmonary environment in CCR2−/− mice results in significantly less lung TRM 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 TRM development through direct interaction with T cells in the lung.
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AUTHOR CONTRIBUTIONS
P.R. Dunbar, S. Takamura, and J.E. Kohlmeier designed the experiments. P.R. Dunbar, E.K. Cartwright, A. N. Wein, T. Tsukamoto, Z.-R.T. Li, N. Kumar, I.E. Uddbäck, S.L. Hayward, S. Ueha, and S. Takamura performed experiments and analyzed data. I.E. Uddbäck and S. Takamura edited the manuscript. P.R. Dunbar and J.E. Kohlmeier wrote the manuscript.
ISSN:1933-0219
1935-3456
1935-3456
DOI:10.1038/s41385-019-0224-7