scholarly journals mSphere of Influence: Innate Immunity at the Maternal-Fetal Barrier

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Kellie Ann Jurado
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Culture System ◽  
Three Dimensional ◽  
Emerging Infectious Diseases ◽  
Innate Immune ◽  
Model Systems ◽  
Immune Control ◽  
Relevant Model ◽  
Link Type

ABSTRACT Kellie Ann Jurado works in the field of emerging infectious diseases. In this mSphere of Influence article, she reflects on how the papers “Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection” (https://doi.org/10.1016/j.chom.2016.03.008) and “A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance” (https://doi.org/10.1126/sciadv.1501462) by Carolyn Coyne’s group have made an impact on her, inspiring her to explore immunity in the placenta by indicating the unique innate immune control elicited at the maternal-fetal barrier as well as by providing physiologically relevant model systems for study.

Virus-associated activation of innate immunity induces rapid disruption of Peyer’s patches in mice

Blood ◽  
2013 ◽  
Vol 122 (15) ◽  
pp. 2591-2599 ◽  
Author(s):  
Simon Heidegger ◽  
David Anz ◽  
Nicolas Stephan ◽  
Bernadette Bohn ◽  
Tina Herbst ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Lymph Nodes ◽  
Immune Activation ◽  
Innate Immune ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Type I ◽  
Peripheral Lymph ◽  
Key Points

Key Points Systemic virus infection leads to rapid disruption of the Peyer’s patches but not of peripheral lymph nodes. Virus-associated innate immune activation and type I IFN release blocks trafficking of B cells to Peyer’s patches.

scholarly journals Preclinical Modelling of PDA: Is Organoid the New Black?

2019 ◽  
Vol 20 (11) ◽  
pp. 2766 ◽  
Author(s):  
Sabrina D’Agosto ◽  
Silvia Andreani ◽  
Aldo Scarpa ◽  
Vincenzo Corbo
Keyword(s):  
Therapeutic Intervention ◽  
Culture System ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Three Dimensional ◽  
Model Systems ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools ◽  
Precision Oncology ◽  
Individual Patient Level

Pancreatic ductal adenocarcinoma (PDA) is a malignancy of the exocrine pancreas with the worst prognosis among all solid tumours, and soon to become the second leading cause of cancer-related deaths. A more comprehensive understanding of the molecular mechanisms underlying this disease is crucial to the development of diagnostic tools as well as to the identification of more effective therapies. High-frequency mutations in PDA occur in “undruggable” genes, and molecular subtyping based on bulk transcriptome analysis does not yet nominate valid therapeutic intervention strategies. Genome-wide sequencing studies have also demonstrated a considerable intra- and inter-patient’s genetic heterogeneity, which further complicate this dire scenario. More than in other malignancies, functionalization of the PDA genome and preclinical modelling at the individual patient level appear necessary to substantially improve survival rates for pancreatic cancer patients. Traditional human PDA models, including monolayer cell cultures and patient-derived xenografts, have certainly led to valuable biological insights in the past years. However, those model systems suffer from several limitations that have contributed to the lack of concordance between preclinical and clinical studies for PDA. Pancreatic ductal organoids have recently emerged as a reliable culture system to establish models from both normal and neoplastic pancreatic tissues. Pancreatic organoid cultures can be efficiently generated from small tissue biopsies, which opens up the possibility of longitudinal studies in individual patients. A proof-of-concept study has demonstrated that patient-derived PDA organoids are able to predict responses to conventional chemotherapy. The use of this three-dimensional culture system has already improved our understanding of PDA biology and promises to implement precision oncology by enabling the alignment of preclinical and clinical platforms to guide therapeutic intervention in PDA.

scholarly journals Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses

2021 ◽  
Vol 17 (9) ◽  
pp. e1009901
Author(s):  
Min Zhao ◽  
Yaolin Zhang ◽  
Xiqin Yang ◽  
Jiayang Jin ◽  
Zhuo Shen ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Nuclear Translocation ◽  
Rna Viruses ◽  
Rna Virus ◽  
Innate Immune ◽  
Type I ◽  
Gene Promoters ◽  
Post Translational Modification

Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity.

scholarly journals Innate immune control of West Nile virus infection

2011 ◽  
Vol 13 (11) ◽  
pp. 1648-1658 ◽  
Author(s):  
Alvaro Arjona ◽  
Penghua Wang ◽  
Ruth R. Montgomery ◽  
Erol Fikrig
Keyword(s):  
West Nile Virus ◽  
Virus Infection ◽  
West Nile Virus Infection ◽  
Innate Immune ◽  
Immune Control ◽  
West Nile

scholarly journals Spatiotemporal dynamics of innate immune signaling via RIG-I–like receptors

2020 ◽  
Vol 117 (27) ◽  
pp. 15778-15788 ◽  
Author(s):  
Katharina Esser-Nobis ◽  
Lauren D. Hatfield ◽  
Michael Gale
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Rna Virus ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Negative Regulator ◽  
Resting Cells ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Irf3 Activation

RIG-I, MDA5, and LGP2 comprise the RIG-I–like receptors (RLRs). RIG-I and MDA5 are essential pathogen recognition receptors sensing viral infections while LGP2 has been described as both RLR cofactor and negative regulator. After sensing and binding to viral RNA, including double-stranded RNA (dsRNA), RIG-I and MDA5 undergo cytosol-to-membrane relocalization to bind and signal through the MAVS adaptor protein on intracellular membranes, thus directing downstream activation of IRF3 and innate immunity. Here, we report examination of the dynamic subcellular localization of all three RLRs within the intracellular response to dsRNA and RNA virus infection. Observations from high resolution biochemical fractionation and electron microscopy, coupled with analysis of protein interactions and IRF3 activation, show that, in resting cells, microsome but not mitochondrial fractions harbor the central components to initiate innate immune signaling. LGP2 interacts with MAVS in microsomes, blocking the RIG-I/MAVS interaction. Remarkably, in response to dsRNA treatment or RNA virus infection, LGP2 is rapidly released from MAVS and redistributed to mitochondria, temporally correlating with IRF3 activation. We reveal that IRF3 activation does not take place on mitochondria but instead occurs at endoplasmic reticulum (ER)-derived membranes. Our observations suggest ER-derived membranes as key RLR signaling platforms controlled through inhibitory actions of LGP2 binding to MAVS wherein LGP2 translocation to mitochondria releases MAVS inhibition to facilitate RLR-mediated signaling of innate immunity.

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