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

ABSTRACT: Lung resident memory CD8 T cells (T_RM) 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_RM following influenza infection. We find that, during the initial appearance of lung T_RM, 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_RM development or maintenance. In contrast, a monocyte deficient pulmonary environment in CCR2^-/- mice results in significantly less lung T_RM 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_RM development through direct interaction with T cells in the lung.

SUBMITTER: Dunbar PR

PROVIDER: S-EPMC6917844 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Dunbar Paul R PR Cartwright Emily K EK Wein Alexander N AN Tsukamoto Tetsuo T Tiger Li Zheng-Rong ZR Kumar Nivedha N Uddbäck Ida E IE Hayward Sarah L SL Ueha Satoshi S Takamura Shiki S Kohlmeier Jacob E JE

Mucosal immunology 20191113 1

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, ...[more]

PMID: 31723250

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Project description:BackgroundThe human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic inflammatory neurodegenerative disease characterized by leukocyte infiltration in the spinal cord. T-lymphocytes are the most important targets of HTLV-1 infection, but monocytes are also infected. Monocytes from HTLV-1-infected individuals exhibit important functional differences compared to cells from uninfected donors. Here, we investigated the effects of cell-cell physical contact and/or secreted factors of HTLV-1-infected cells in monocyte activation and differentiation.MethodsThe THP-1 human monocytic cell line was co-cultured with a human cell line transformed by HTLV-1 (MT-2) for 6 days. To determine the effects of co-culturing HTLV-1-infected cells in THP-1 monocytes cells were characterized by flow cytometry, immunofluorescence microscopy, and real-time PCR. Computational analysis of published transcriptomic datasets was realized to compare molecular profiles of macrophages and mononuclear cells from HTLV-1 carriers.ResultsCo-culture of monocytes with HTLV-1-infected cells induced macrophage differentiation and upregulation of typical macrophages-associated molecules (HLA-DR, CD80, and CD86), increased cytokine (TNFα, IL-6, and IL-1β) levels and their coding genes expression. Consistently, published transcriptomic datasets showed changes in important genes associated with inflammation during HAM/TSP in patients. The presence of HTLV-1-infected cells in the culture also induced significant upregulation of Interferon Stimulated Genes (ISG), indicating viral infection. Monocyte activation and differentiation into pro-inflammatory macrophages occurred in a cell-to-cell contact-independent manner, suggesting the role of factors secreted by infected cells.ConclusionsTogether, our results indicated that HTLV-1-infected cells induced monocyte differentiation into macrophages inflammatory, predominantly.

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

Publications

Pulmonary monocytes interact with effector T cells in the lung tissue to drive T<sub>RM</sub> differentiation following viral infection.

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