The specifics of innate immune memory

doi:10.1126/science.abc2660

GSTDTAP > 气候变化

DOI	10.1126/science.abc2660
	The specifics of innate immune memory
	Jorge Domínguez-Andrés; Mihai G. Netea
	2020-06-05
发表期刊	Science
出版年	2020
英文摘要	One of the most important traits of immune host defense against pathogens is memory, which improves survival if the same pathogen is reencountered. However, immune memory can also be deleterious, driving autoimmune diseases and the rejection of transplanted organs. Memory characteristics have been considered a fundamental property of adaptive immune cells such as T and B lymphocytes ([ 1 ][1]). However, innate immune cells such as myeloid cells and natural killer (NK) cells can also adapt to previous encounters with pathogens through epigenetic, transcriptional, and functional reprogramming, called trained immunity ([ 2 ][2]). The discovery of this innate immune memory emerged from studies with live vaccines and was described as being largely nonspecific ([ 3 ][3]). On page 1122 of this issue, Dai et al. ([ 4 ][4]) reveal that monocytes and macrophages acquire specific memory and induce organ rejection in mice, which could be prevented to improve transplantation outcomes. Dai et al. use a series of elegant transplant models in different mouse strains, showing that the rejection of grafts is maintained in individuals without a functional adaptive immune response. Graft rejection was mediated by monocytes and macrophages, which retained their memory functions several weeks after the encounter with antigens from the donor. This specific memory response was dependent on paired immunoglobulin-like receptor-A (PIR-A), an activation receptor expressed by B cells and myeloid lineage cells, which can recognize major histocompatibility complex class I (MHC-I) molecules (see the figure). MHC-I expressed on the surface of most nucleated cells presents peptide fragments of endogenous proteins, which can be subsequently recognized as antigens by the immune cells of the recipient of a transplant and cause its rejection ([ 5 ][5]). Blocking or deleting PIR-A receptors impaired the recognition of MHC-I–peptide complexes expressed in the donor cells, which decreased the rejection of transplanted hearts and kidneys and improved outcomes. This specificity of innate immune memory in mouse myeloid cells described by Dai et al. is reminiscent of memory characteristics of innate immune cells of several invertebrates, which lack an adaptive immune system. These include diversification of genes encoding fibrinogen-related proteins (FREPs) in mollusks ([ 6 ][6]) and scavenger receptor cysteine-rich proteins in echinoderms ([ 7 ][7]) or alternative splicing of the immunoglobulin (Ig) domain–encoding gene Down syndrome cell adhesion molecule ( Dscam ) in insects ([ 5 ][5]). It is important to note that in both vertebrates and invertebrates, the Ig superfamily of molecules is often the pillar mediating specificity of the innate immune memory responses. Indeed, PIR-A, B cell receptors, immunoglobulins, and T cell receptors share a similar type of structure, which argues for an evolutionary continuum of memory specificity in innate and adaptive immune responses. Ig-based specific immune responses complement the more primitive nonspecific trained immunity-mediated memory ([ 8 ][8]). The increased responsiveness provided by trained immunity after certain infections or vaccinations can induce protection against both specific and heterologous infections ([ 9 ][9], [ 10 ][10]). Yet, in conditions characterized by excessive immune responses, such as inflammatory and autoimmune diseases and organ transplant rejection, enhanced innate immune responses can aggravate the pathological consequences of inflammation. It is crucial to know the roles played by innate immune cells in transplant rejection, in order to target it and improve survival. The findings of Dai et al. have several implications that go beyond transplantation. If monocytes and macrophages can develop specific memory to MHC-I–presented antigens, this reveals possible therapeutic approaches in organ transplantation, but also autoimmune and inflammatory diseases. In addition, it is intriguing to hypothesize whether specific innate immune memory responses could also form against pathogens, as proposed for NK cells in response to viral infections ([ 2 ][2]). Macrophages are heterogeneous tissue-resident cells: Yolk sac– and fetal liver monocyte–derived tissue-resident macrophages colonize different tissues during embryonic development ([ 11 ][11]). These are long-lived and able to self-renew, so the specific characteristics of these macrophages rely on their niche ([ 11 ][11]). For example, lung macrophages are exposed to airway antigens, whereas Kupffer cells in the liver are exposed to gut-derived molecules ([ 12 ][12]). The phenotype of a microglial cell in the brain greatly differs from that of a peritoneal macrophage ([ 11 ][11]). The potential ability of these and other myeloid cell subsets to develop different types of immunological memory to antigens could offer additional evidence for their different functions across tissues and help to explain the development of different types of memory responses to the same antigens in different locations. In this context, it will be crucial to address if the antigen-specific responses by myeloid cells can also be inhibitory and may be involved in the development of immunological tolerance leading to the lack of responsiveness against harmless molecules such as antigens expressed by commensal bacteria, or self-antigens. Immunological tolerance prevents harmful immune responses in the host, whereas failure of these mechanisms results in tissue damage and autoimmune responses ([ 13 ][13]). Indeed, polymorphisms in genes of the human leukocyte antigen (HLA) system, the human version of MHC, are associated with celiac disease, inflammatory bowel disease, rheumatoid arthritis, psoriasis, type 1 diabetes, and multiple sclerosis ([ 14 ][14], [ 15 ][15]). Additional studies have found genetic associations between MHC-I and infectious diseases such as HIV, human hepatitis B virus, and tuberculosis ([ 14 ][14]). ![Figure][16] Different forms of innate immunological memory Some myeloid cells can develop memory. After a first stimulus, retained epigenetic changes can facilitate the production of cytokines after a nonspecific stimulus (trained immunity). Macrophages can also develop specific memory through paired immunoglobulin-like receptor-A (PIR-A) specificity to antigens presented by major histocompatibility complex class I (MHC-I). GRAPHIC: JOSHUA BIRD/ SCIENCE If monocytes and macrophages develop antigen-specific memory to antigens presented by donor-derived MHC-I molecules, it is likely that these and other myeloid cells can develop immunological memory to self- and nonself antigens of different sources. Given the variety of receptors expressed by the different types of myeloid cells, the implications of these mechanisms could encompass many processes beyond organ transplantation, including the response to pathogens, vaccines, inflammatory and autoimmune diseases, or the development of allergies. Dai et al. identified several families of polymorphic Ig superfamily receptors that could bind to MHC-I molecules. The extension of this search to other receptors that can bind antigens of a different nature could lead to the identification of other structures with the potential to trigger or block antigen-specific memory in myeloid cells, potentially offering a new set of targets for immunotherapy. 1. [↵][17]1. F. A. 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领域	气候变化 ; 资源环境
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/273428
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jorge Domínguez-Andrés,Mihai G. Netea. The specifics of innate immune memory[J]. Science,2020.
APA	Jorge Domínguez-Andrés,&Mihai G. Netea.(2020).The specifics of innate immune memory.Science.
MLA	Jorge Domínguez-Andrés,et al."The specifics of innate immune memory".Science (2020).