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Two kinds of macrophage memory: innate and adaptive immune-like macrophage memory

Cellular & Molecular Immunology volume 19, pages 852–854 (2022)Cite this article

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It is believed that the adaptive immune system responds to nonself entities with its specificity and memory properties. In contrast, the innate immune system lacks adaptive characteristics. Whether innate immune cells can generate adaptive immune features has always been an unanswered question. However, an increasing number of studies have shown that innate immune cells exhibit antigen specificity and memory characteristics similar to those of adaptive immune cells after first-time stimulation. Studies of natural killer cells (NK cells) with immune memory were reported as early as 2006 [1]. O’Leary et al. found that mouse NK cells can trigger hapten-specific contact hypersensitivity with memory properties [1]. Subsequently, memory NK cells could be detected in mice infected with mouse cytomegalovirus, further strengthening the conclusion that NK cells have immune memory. Subsequently, additional studies have shown that NK cells have immune memory for various viruses, such as cytomegalovirus, vaccinia virus, and influenza virus [2,3,4].

Similarly, Dai et al. also showed that monocytes and macrophages primed with alloantigen acquired a specific memory for that antigen and were able to rapidly promote the rejection of allogeneic grafts [9]. They identified that paired immunoglobulin-like receptor-A, an MHC-I receptor, was necessary for the primed macrophage-mediated memory response in mice [9]. Further studies have shown that the acquired so-called adaptive immune ability of primed macrophages requires the help of CD4+ T cells during the priming phase [5, 7]. In another experimental model, the generation of antigen-specific memory in mouse alveolar macrophages after adenovirus infection required the support role of CD8+ T cells and their secreted IFN-γ, as reported by Yao et al. [6]. The generation of macrophage antigen-specific memory in different disease models may require the assistance of various types of T cells. The requirements for CD4+ or CD8+ T cells to promote memory macrophage formation in different conditions must be clarified. Nevertheless, these studies clearly demonstrated that activated macrophages, with the help of CD4+ T cells, can gain the ability to reject allogeneic grafts with a certain memory and specificity in the subsequent immune response. This observation provides a new fundamental basis for challenging the dogma that macrophages solely have innate features in animals with an adaptive immune system.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation for Key Programs (31930041, YZ), Knowledge Innovation Program of the Chinese Academy of Sciences (XDA16030301, YZ), and National Key Research and Development Program of China (2017YFA0105002, 2017YFA0104402, YZ).

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Authors and Affiliations

  1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

    Changhong Wu, Yanan Xu & Yong Zhao

  2. Cunji Medical School, University of Chinese Academy of Sciences, Beijing, China

    Changhong Wu & Yong Zhao

  3. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China

    Yong Zhao

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  1. Changhong Wu
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YZ conceived of this commentary. CW and YZ wrote the manuscript. YX revised the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Yong Zhao.

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Wu, C., Xu, Y. & Zhao, Y. Two kinds of macrophage memory: innate and adaptive immune-like macrophage memory. Cell Mol Immunol 19, 852–854 (2022). https://doi.org/10.1038/s41423-022-00885-y

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