Antigen-specific CD4+ T cells promote monocyte recruitment and differentiation into glycolytic lung macrophages to control Mycobacterium tuberculosis.
Although lung myeloid cells provide an intracellular niche for Mycobacterium tuberculosis (Mtb), CD4+ T cells limit Mtb growth in these cells to protect the host. The CD4+ T cell activities including interferon-γ (IFN-γ) production that account for this protection are poorly understood. Using intrav...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013208 |
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| Summary: | Although lung myeloid cells provide an intracellular niche for Mycobacterium tuberculosis (Mtb), CD4+ T cells limit Mtb growth in these cells to protect the host. The CD4+ T cell activities including interferon-γ (IFN-γ) production that account for this protection are poorly understood. Using intravenous antibody labeling and lineage-tracing reporter mice, we show that monocyte-derived macrophages (MDMs), rather than phenotypically similar monocytes or dendritic cells, are preferentially infected with Mtb in murine lungs. MDMs were recruited to the lungs by Mtb-specific CD4+ T cells via IFN-γ, which promoted the extravasation of monocyte precursors from the blood. It was possible that CD4+ T cells recruited infectable MDMs because these cells are uniquely poised to receive cognate MHCII-mediated help to control intracellular bacteria. Mice with MHCII deficiency in monocyte-derived cells had normal Mtb-specific CD4+ T cell activation, expansion and differentiation but the CD4+ T cells were unable to attenuate Mtb growth. Using single cell RNA sequencing, we showed that MDMs receiving cognate MHCII-mediated help from CD4+ T cells upregulated glycolytic genes associated with Mtb control. Overall, the results indicate that CD4+ T cells recruit infectable MDMs to the lungs and then trigger glycolysis-dependent bacterial control in the MDMs by engaging their MHCII-bound Mtb peptides. Moreover, the results suggest that cognate MHCII-mediated help to promote MDM glycolysis is an essential, IFN-γ-independent effector function of Mtb-specific CD4+ T cells. |
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| ISSN: | 1553-7366 1553-7374 |