Immunological Memory in Innate Immunity

Netea, Mihai G.

doi:10.1159/000357283

Cited by 17 publications

(17 citation statements)

References 8 publications

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“…Those protective mechanisms were so strong that few additional transcriptional changes could be detected after VHSVS re-infection in the VHSVS+ phenotype. These findings also point to new lines of research into the newly described associations of the multigene families in fish with trained immunity described in mammals [ 3 , 11 , 12 , 27 ].…”

Section: Introductionmentioning

confidence: 62%

“…Innate memories may complement the well-known adaptive memory responses, such as viral-specific antibodies (Abs). Thus, adaptive features such as the innate memories typically found in invertebrates, are now being increasingly found in mammalians [ 1 , 2 , 3 , 4 , 5 ]. Given that fish are primitive vertebrates with an early immunological system (absence of IgG switch or IgM maturation, mucosal IgT/IgZ, phagocytic B-cells, etc), they might rely more on innate rather than adaptive immune responses to tackle viral diseases [ 6 ], however this notion has to be proven.…”

Section: Introductionmentioning

confidence: 99%

“…Typical adaptive features of innate immunity known as "trained immunity" are recently been reported in mammalians [ 1 , 2 , 3 , 4 , 5 ]. To date, the main features of such immunity are as follows: i) it confers protection by B-/T-cell-independent mechanisms; ii) it involves macrophage/natural killer (NK) cells [ 11 – 13 ] ; iii) it remembers cross-protection to homologous and heterologous pathogens; iv) it enhances pathogen detection by means of several pattern recognition receptors and subsequent inflammatory responses [ 2 , 14 ]; and v) it generates gene variation by epigenetic reprogramming (alternative splicing, DNA/histone modifications, miRNA, etc) rather than by genetic recombination [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Innate Multigene Family Memories Are Implicated in the Viral-Survivor Zebrafish Phenotype

Estepa

Coll

2015

PLoS ONE

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Since adaptive features such as memory were discovered in mammalian innate immunity, interest in the immunological status of primitive vertebrates after infections has grown. In this context, we used zebrafish (Danio rerio), a primitive vertebrate species suited to molecular and genetic studies to explore transcriptional memories of the immune system in long-term survivors of viral haemorrhagic septicemia virus infections. Immune-gene targeted microarrays designed in-house, multipath genes, gene set enrichment, and leading-edge analysis, reveal unexpected consistent correlations between the viral-survivor phenotype and several innate multigene families. Thus, here we describe in survivors of infections the upregulation of the multigene family of proteasome subunit macropains, zebrafish-specific novel gene sets, mitogen activated protein kinases, and epidermal growth factor. We also describe the downregulation of the multigene families of c-reactive proteins, myxovirus-induced proteins and novel immunoglobulin-type receptors. The strength of those immunological memories was reflected by the exceptional similarity of the transcriptional profiles of survivors before and after re-infection compared with primary infected fish. On the other hand, the high levels of neutralizing antibodies in the blood plasma of survivors contrasted with the depletion of transcripts specific for most cell types present in lymphoid organs. Therefore, long-term survivors maintained unexpected molecular/cellular memories of previous viral encounters by modulating the expression levels of innate multigene families as well as having specific adaptive antibodies. The implications of the so-called "trained immunity" for future research in this field are also discussed.

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Section: Introductionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Innate Multigene Family Memories Are Implicated in the Viral-Survivor Zebrafish Phenotype

Estepa

Coll

2015

PLoS ONE

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“…Conventionally, memory responses, the basis of acquired resistance and vaccines, were considered the hallmark of antigen-specific T cells and B cells. Increasing evidence now suggests that cells of the innate immune system can also develop memory-like responses, or so-called 'trained immunity' 45,46 . PRRs expressed by cells of the innate immune system provide one mechanism for the specificity, albeit not the antigen specificity, of the response.…”

Section: Macrophage Activation States and Acquired Resistancementioning

confidence: 99%

Innate cell communication kick-starts pathogen-specific immunity

et al. 2016

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Innate cells are responsible for the rapid recognition of infection and mediate essential mechanisms of pathogen elimination, and also facilitate adaptive immune responses. We review here the numerous intricate interactions among innate cells that initiate protective immunity. The efficient eradication of pathogens depends on the coordinated actions of multiple cells, including innate cells and epithelial cells. Rather than acting as isolated effector cells, innate cells are in constant communication with other responding cells of the immune system, locally and distally. These interactions are critically important for the efficient control of primary infections as well for the development of ‘trained’ innate cells that facilitate the rapid elimination of homologous or heterologous infections.

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“…Thus, previous examples of polyclonal fish B-cell activation have been described in which salmonid B-cells stimulated by mitogens not only proliferated but also increased total IgM serum levels ( 42 – 46 ). Other alternative explanations may be related to the fact that pathogen cross-reactivity is one of the main characteristics of mammalian trained immunity ( 47 – 53 ). Thus, growing evidence in favor of pathogen cross-reactivity, is now being increasingly identified in mammalians innate responses ( 50 , 51 , 53 – 55 ) elicited by some vaccines ( 56 , 57 ).…”

Section: Discussionmentioning

confidence: 99%

Herpesvirus Infection Induces both Specific and Heterologous Antiviral Antibodies in Carp

Coll

2018

Front. Immunol.

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IgM antibody diversity induced by viral infection in teleost fish sera remains largely unexplored despite several studies performed on their transcript counterparts in lymphoid organs. Here, IgM binding to microarrays containing ~20,000 human proteins was used to study sera from carp (Cyprinus carpio) populations having high titers of viral neutralization in vitro after surviving an experimental infection with cyprinid herpes virus 3 (CyHV-3). The range of diversity of the induced antibodies was unexpectedly high, showing CyHV-3 infection-dependent, non-specific IgM-binding activity of a ~20-fold wider variety than that found in sera from healthy carp (natural antibodies) with no anti-CyHV-3 neutralization titers. An inverse correlation between the IgM-binding levels in healthy versus infection-survivor/healthy ratios suggests that an infection-dependent feed back-like mechanism may control such clonal expansion. Surprisingly, among the infection-expanded levels, not only specific anti-frgIICyHV-3 and anti-CyHV-3 IgM-binding antibodies but also antibodies recognizing recombinant fragment epitopes from heterologous fish rhabdoviruses were detected in infection-survivor carp sera. Some alternative explanations for these findings in lower vertebrates are discussed.

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Immunological Memory in Innate Immunity

Cited by 17 publications

References 8 publications

Innate Multigene Family Memories Are Implicated in the Viral-Survivor Zebrafish Phenotype

Innate Multigene Family Memories Are Implicated in the Viral-Survivor Zebrafish Phenotype

Innate cell communication kick-starts pathogen-specific immunity

Herpesvirus Infection Induces both Specific and Heterologous Antiviral Antibodies in Carp

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