Cell
Volume 175, Issue 6, 29 November 2018, Pages 1634-1650.e17
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Article
Induction of Autonomous Memory Alveolar Macrophages Requires T Cell Help and Is Critical to Trained Immunity

https://doi.org/10.1016/j.cell.2018.09.042Get rights and content
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Highlights

  • Respiratory viral infection induces lasting innate memory alveolar macrophages

  • Memory alveolar macrophages develop and sustain independently of blood monocytes

  • Adaptive T cells render innate macrophage memory via IFN-γ production

  • Memory macrophages mediate trained anti-bacterial immunity via enhanced neutrophilia

Summary

Innate immune memory is an emerging area of research. However, innate immune memory at major mucosal sites remains poorly understood. Here, we show that respiratory viral infection induces long-lasting memory alveolar macrophages (AMs). Memory AMs are programed to express high MHC II, a defense-ready gene signature, and increased glycolytic metabolism, and produce, upon re-stimulation, neutrophil chemokines. Using a multitude of approaches, we reveal that the priming, but not maintenance, of memory AMs requires the help from effector CD8 T cells. T cells jump-start this process via IFN-γ production. We further find that formation and maintenance of memory AMs are independent of monocytes or bone marrow progenitors. Finally, we demonstrate that memory AMs are poised for robust trained immunity against bacterial infection in the lung via rapid induction of chemokines and neutrophilia. Our study thus establishes a new paradigm of immunological memory formation whereby adaptive T-lymphocytes render innate memory of mucosal-associated macrophages.

Keywords

innate immune memory
trained immunity
memory alveolar macrophages
T-cell help
CD8 T cells
viral infection
IFN-γ
Streptococcus pneumoniae
lung

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