Constitutive immune mechanisms: mediators of host defence and immune regulation

Paludan, Søren R; Pradeu, Thomas; Masters, Seth L.; Mogensen, Trine H.

doi:10.1038/s41577-020-0391-5

Cited by 200 publications

(155 citation statements)

References 188 publications

(245 reference statements)

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“…In contrast, constitutive innate immune mechanisms have the advantage of an immediate host defense against invading pathogens. A large number of constitutive mechanisms of innate immunity have been described including chemical barriers, antimicrobial peptides, basal autophagy or proteasomal degradation [ 2 ]. One drawback of these mechanisms is a lack of specificity.…”

Section: Introductionmentioning

confidence: 99%

Intrinsic Immune Mechanisms Restricting Human Cytomegalovirus Replication

Schilling¹,

Scherer²,

Stamminger³

2021

Viruses

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Cellular restriction factors (RFs) act as important constitutive innate immune barriers against viruses. In 2006, the promyelocytic leukemia protein was described as the first RF against human cytomegalovirus (HCMV) infection which is antagonized by the viral immediate early protein IE1. Since then, at least 15 additional RFs against HCMV have been identified, including the chromatin regulatory protein SPOC1, the cytidine deaminase APOBEC3A and the dNTP triphosphohydrolase SAMHD1. These RFs affect distinct steps of the viral replication cycle such as viral entry, gene expression, the synthesis of progeny DNA or egress. This review summarizes our current knowledge on intrinsic immune mechanisms restricting HCMV replication as well as on the viral strategies to counteract the inhibitory effects of RFs. Detailed knowledge on the interplay between host RFs and antagonizing viral factors will be fundamental to develop new approaches to combat HCMV infection.

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Section: Introductionmentioning

confidence: 99%

Intrinsic Immune Mechanisms Restricting Human Cytomegalovirus Replication

Schilling¹,

Scherer²,

Stamminger³

2021

Viruses

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show abstract

“…In addition to peptides' sequence-based recognition features, numerous other factors such as costimulation, proliferation, cytotoxicity and cytokine production are evidently associated with immunogenicity 1 . These factors collectively define the magnitude and shape of the immune response and determine whether a response is elicited 10 . Consequently, identification of 'immunogenic' peptides has proven to be more challenging than identification of peptides presented by MHC molecules 11 .…”

Section: Introductionmentioning

confidence: 99%

Evaluating performance of existing computational models in predicting CD8+ T cell pathogenic epitopes and cancer neoantigens

Buckley

Lee

et al. 2020

Preprint

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T cell recognition of a cognate peptide-MHC complex (pMHC) presented on the surface of infected or malignant cells are of utmost importance for mediating robust and long-term immune responses. Accurate predictions of cognate pMHC targets for T Cell Receptors (TCR) would greatly facilitate identification of vaccine targets for both pathogenic diseases as well as personalized cancer immunotherapies. Predicting immunogenic epitopes therefore has been at the centre of intensive research for the past decades but has proven challenging. Although numerous models have been proposed, performance of these models has not been systematically evaluated and their success rate in predicting epitopes for humans has not been measured and compared.In this study, we curate and present a ‘standard-dataset’ of class I MHC epitopes for evaluating the performance of immunogenicity classifiers. Using this data, we present a systematic evaluation of performance of several publicly available models which are commonly used to predict CD8+ T cell epitopes in the context of both pathogens and cancers. The benchmarking is performed in two different settings: a pan-HLA setting in which all models are trained and evaluated by a pool of peptides from multiple HLA types, and a HLA-specific setting in which models are trained and evaluated by peptides from HLA-A02:01. In the pan-HLA setting, we observe that the best performing model achieves 75.6% accuracy suggesting considerable room for improvement. In the HLA-specific setting we observe a substantial reduction in performance with a mean of −11.9%. Our work shows that existing models exhibit suboptimal performance for predicting immunogenic cancer neoantigens. We then further interrogate the underlying problems of model predictions and highlight HLA-bias as a main source of variation amongst other issues associated with the design of models and/or to their training data.

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“…At defined phases of the annual cycle, such as migration, molt, or reproductive activation, several measures were taken to assess immunity ( Versteegh et al, 2014 ). The study focused on constitutive immunity as a general, first line of defense, including against viral and bacterial pathogens ( Paludan et al, 2020 ). Most measures differed across the birds’ annual cycle, as well as between populations.…”

Section: Seasonal Within-host Changes: Photoperiodism and Circannual mentioning

confidence: 99%

Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19

et al. 2021

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Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

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Constitutive immune mechanisms: mediators of host defence and immune regulation

Cited by 200 publications

References 188 publications

Intrinsic Immune Mechanisms Restricting Human Cytomegalovirus Replication

Intrinsic Immune Mechanisms Restricting Human Cytomegalovirus Replication

Evaluating performance of existing computational models in predicting CD8+ T cell pathogenic epitopes and cancer neoantigens

Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19

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