Innate (learned) memory

Al, Burcu; Suen, Tsz Kin; Placek, Katarzyna; Netea, Mihai G.

doi:10.1016/j.jaci.2023.06.014

Cited by 17 publications

(17 citation statements)

References 216 publications

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“…The trained immunity phenomenon was recognized with the realization that live attenuated vaccines, most notably BCG, in addition to the intended protection against the vaccine pathogen, conferred heterologous protection leading to reduced incidence of several common diseases in BCG-vaccinated children [33, 34]. This protection has since been found to be driven by metabolic and epigenetic changes in innate immune cell precursors in the bone marrow (central trained immunity) and in differentiated circulating or tissue resident cells (peripheral trained immunity), leading to altered response quality and quantity upon secondary challenges [8]. Much effort has been put into deciphering the molecular signatures defining different forms of trained immunity, but little is still known about the specific requirements for when trained immunity is triggered in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…During the resolution phase after an infection, expanded populations of specific B and T cells contract and leave behind memory cells with heightened activation potential. Recent advances however have shown that the spectrum of lasting infection-or vaccine-induced immune protection is broader than previously appreciated, and may include several forms of imprinted memory-like functions driven by metabolic and epigenetic changes in innate immune cell populations (trained immunity) [8]. In contrast to adaptive B and T cell memory, imprinted innate responses are non-specific and thus confer protection against both homologous and heterologous infections.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to adaptive B and T cell memory, imprinted innate responses are non-specific and thus confer protection against both homologous and heterologous infections. Although our knowledge is clearly still limited, trained immunity has been extensively studied in myeloid populations like monocytes/macrophages and their precursors in the bone marrow, and has also been described in lymphoid NK cells, ILCs and γδ T cells [8].…”

Section: Introductionmentioning

confidence: 99%

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Protection conferred by intraperitoneal Group AStreptococcusimmunization relies on macrophages and IFN-γ but not on concurrent adaptive immune responses

Emami,

Westerlund,

Converso

et al. 2023

Preprint

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Group AStreptococcus(GAS;Streptococcus pyogenes) is an important bacterial pathogen estimated to cause over 700 million superficial infections and around 500.000 deaths due to invasive disease or severe post-infection sequelae in the world yearly. In spite of this major impact on society, there is currently no vaccine available against this bacterium. GAS strains can be separated into >200 distinctemm(M)-types, and protective immunity against GAS is believed to in part be dependent on type-specific antibodies. Here, we analyze the nature of protective immunity generated against GAS in a model of intraperitoneal immunization in mice. We demonstrate that multiple immunizations are required for the ability to survive a subsequent lethal challenge, and although significant levels of GAS-specific antibodies are produced, these are redundant for protection. Instead, our data show that the immunization-dependent protection in this model is induced in the absence of B and T cells, is accompanied by an altered cytokine profile upon subsequent infection and requires macrophages and the macrophage-activating cytokine IFN-γ. To our knowledge these findings are the first to suggest that GAS has the ability to induce forms of trained innate immunity. Taken together, the current study reveals a novel mechanism of the innate immune system in response to GAS infections that potentially could be leveraged for future development of effective vaccines.Author summaryThe bacterium Group A Streptococcus (GAS) causes many hundred million infections and around 500.000 deaths in the world every year. GAS can give rise to a wide spectrum of diseases ranging from mild strep throat to life-threatening necrotizing fasciitis (often referred to as “flesh-eating disease”). There is currently no vaccine available for this pathogen, much due to our incomplete knowledge of how the immune system reacts to different GAS infections, what immune responses are in fact required for long-term protection and how these are generated. Here we show that protective immunity arising after immunization through the intraperitoneal (ip) cavity requires multiple injections using heat killed GAS. Surprisingly, although typical adaptive immune responses are activated and generate production of GAS-specific antibodies these are redundant for protection, which instead hinges on macrophages and the cytokine IFN-γ. Our findings suggest that ip GAS immunizations trigger what is known as ‘trained immunity’, where innate immune cells become imprinted to respond with increased efficiency towards subsequent infection. Overall, these observations highlight a previously unknown ability of GAS to induce non-canonical forms of protective immunity, discoveries that may significantly contribute to our thinking about how the immune system reacts to such infections and broaden the scope for future vaccine strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protection conferred by intraperitoneal Group AStreptococcusimmunization relies on macrophages and IFN-γ but not on concurrent adaptive immune responses

Emami,

Westerlund,

Converso

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Several innate immune cells such as monocytes, macrophages, neutrophils, dendritic cells, natural killer cells, innate lymphoid cells and γδ-T cells are involved in trained immunity and have been mostly studied to date. 32,33 Furthermore, the induction of trained immunity has been reported in non-immune cell types such as mesenchymal stem cells, epithelial cells and fibroblasts. 32,33 BCG vaccine and β-glucan (a cell wall component of Candida albicans) also induce epigenetic changes and metabolic rewiring in haematopoietic stem cells, which undergo increased expansion and myelopoiesis.…”

Section: Types Of Cells Involved In Trained Immunitymentioning

confidence: 99%

“…32,33 Furthermore, the induction of trained immunity has been reported in non-immune cell types such as mesenchymal stem cells, epithelial cells and fibroblasts. 32,33 BCG vaccine and β-glucan (a cell wall component of Candida albicans) also induce epigenetic changes and metabolic rewiring in haematopoietic stem cells, which undergo increased expansion and myelopoiesis. 5,6 Trained haematopoietic stem cells then differentiate in epigenetically-modified monocytes allowing the persistence of the effect despite their short half-life in the circulation.…”

Section: Types Of Cells Involved In Trained Immunitymentioning

confidence: 99%

The impact of trained immunity in respiratory viral infections

Piret,

Boivin

2024

Reviews in Medical Virology

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Epidemic peaks of respiratory viruses that co‐circulate during the winter‐spring seasons can be synchronous or asynchronous. The occurrence of temporal patterns in epidemics caused by some respiratory viruses suggests that they could negatively interact with each other. These negative interactions may result from a programme of innate immune memory, known as trained immunity, which may confer broad protective effects against respiratory viruses. It is suggested that stimulation of innate immune cells by a vaccine or a pathogen could induce their long‐term functional reprogramming through an interplay between metabolic and epigenetic changes, which influence the transcriptional response to a secondary challenge. During the coronavirus disease 2019 pandemic, the circulation of most respiratory viruses was prevented by non‐pharmacological interventions and then resumed at unusual periods once sanitary measures were lifted. With time, respiratory viruses should find again their own ecological niches. This transition period provides an opportunity to study the interactions between respiratory viruses at the population level.

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