ILT7 activation and plasmacytoid dendritic cell response are governed by BST2 determinants that are structurally-distinct

AbstractThe interaction of the human pDC receptor ILT7 with its ligand, BST2, significantly regulates pDC’s TLR-induced innate immune responses. This interaction has critical biological consequences, yet, its structural requirements are not fully characterized. The BST2 ectodomain can be divided in structurally and functionally distinct regions; while the coiled-coil region contains a newly-defined ILT7 binding surface, the N-terminal region appears to negatively modulate ILT7 activation. A stable BST2 homodimer binds to ILT7 but post-binding events associated to the unique BST2 coiled-coil plasticity are required to trigger receptor signaling. Hence, BST2 with an unstable or with a rigid coiled-coil fails to activate ILT7, whereas mutations in the N-terminal region enhance activation. Importantly, the biological relevance of these newly defined domains of BST2 is underscored by the identification of mutations with opposed potential to activate ILT7, which are selected under pathological malignant conditions.

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Structural basis of NLR activation and innate immune signalling in plants

Immunogenetics ◽

10.1007/s00251-021-01242-5 ◽

2022 ◽

Author(s):

Natsumi Maruta ◽

Hayden Burdett ◽

Bryan Y. J. Lim ◽

Xiahao Hu ◽

Sneha Desa ◽

...

Keyword(s):

Immune Responses ◽

Interleukin 1 ◽

Three Dimensional ◽

Coiled Coil ◽

Innate Immune ◽

Structural Basis ◽

Innate Immune Responses ◽

Oligomeric State ◽

Coiled Coil Domain ◽

The Family

AbstractAnimals and plants have NLRs (nucleotide-binding leucine-rich repeat receptors) that recognize the presence of pathogens and initiate innate immune responses. In plants, there are three types of NLRs distinguished by their N-terminal domain: the CC (coiled-coil) domain NLRs, the TIR (Toll/interleukin-1 receptor) domain NLRs and the RPW8 (resistance to powdery mildew 8)-like coiled-coil domain NLRs. CC-NLRs (CNLs) and TIR-NLRs (TNLs) generally act as sensors of effectors secreted by pathogens, while RPW8-NLRs (RNLs) signal downstream of many sensor NLRs and are called helper NLRs. Recent studies have revealed three dimensional structures of a CNL (ZAR1) including its inactive, intermediate and active oligomeric state, as well as TNLs (RPP1 and ROQ1) in their active oligomeric states. Furthermore, accumulating evidence suggests that members of the family of lipase-like EDS1 (enhanced disease susceptibility 1) proteins, which are uniquely found in seed plants, play a key role in providing a link between sensor NLRs and helper NLRs during innate immune responses. Here, we summarize the implications of the plant NLR structures that provide insights into distinct mechanisms of action by the different sensor NLRs and discuss plant NLR-mediated innate immune signalling pathways involving the EDS1 family proteins and RNLs.

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Dissection of measles virus V protein in relation to its ability to block alpha/beta interferon signal transduction

Journal of General Virology ◽

10.1099/vir.0.80308-0 ◽

2004 ◽

Vol 85 (10) ◽

pp. 2991-2999 ◽

Cited By ~ 106

Author(s):

Shinji Ohno ◽

Nobuyuki Ono ◽

Makoto Takeda ◽

Kaoru Takeuchi ◽

Yusuke Yanagi

Keyword(s):

Immune Responses ◽

Measles Virus ◽

Viral Infections ◽

Terminal Region ◽

Innate Immune ◽

Innate Immune Responses ◽

Wild Type ◽

Antagonist Activity ◽

V Protein ◽

P Protein

Interferon (IFN)-α and -β are the main cytokines for innate immune responses against viral infections. To replicate efficiently in the hosts, viruses have evolved various countermeasures to the IFN response. The V protein of measles virus (MV) has been shown to block IFN-α/β signalling. Here, the wild-type IC-B strain of MV was shown to grow comparably in the presence and absence of IFN-α, whereas replication of the Edmonston tag strain recovered from cloned DNA was strongly suppressed in its presence. The V protein of the IC-B strain, but not the Edmonston tag strain, blocked IFN-α signalling. The V protein of the Edmonston strain from the ATCC also inhibited IFN-α signalling. There were three amino acid differences between the V proteins of the Edmonston ATCC and tag strains, and substitutions of both residues at positions 110 and 272 were required for the Edmonston ATCC V protein to lose IFN-antagonist activity. The P protein of the IC-B strain, which shares the N-terminal 231 aa residues with the V protein, also inhibited IFN-α signalling. Indeed, fragments comprising only those 231 residues of the IC-B and Edmonston ATCC V proteins, but not the Edmonston tag V protein, were able to block IFN-α signalling. However, the N-terminal region of the Edmonston tag V protein, when attached to the C-terminal region of the Edmonston ATCC V protein, inhibited IFN-α signalling. Taken together, our results indicate that both the N- and C-terminal regions contribute to the IFN-antagonist activity of the MV V protein.

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Impaired Plasmacytoid Dendritic Cell Innate Immune Responses in Patients with Herpes Virus-Associated Acute Retinal Necrosis

The Journal of Immunology ◽

10.4049/jimmunol.179.6.4219 ◽

2007 ◽

Vol 179 (6) ◽

pp. 4219-4230 ◽

Cited By ~ 25

Author(s):

Nicolai A. Kittan ◽

Antonio Bergua ◽

Sabrina Haupt ◽

Norbert Donhauser ◽

Philipp Schuster ◽

...

Keyword(s):

Dendritic Cell ◽

Immune Responses ◽

Herpes Virus ◽

Plasmacytoid Dendritic Cell ◽

Innate Immune ◽

Acute Retinal Necrosis ◽

Innate Immune Responses ◽

Herpès Virus

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Oral Immune Activation by Disgust and Disease-Related Pictures

Journal of Psychophysiology ◽

10.1027/0269-8803/a000143 ◽

2015 ◽

Vol 29 (3) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Richard J. Stevenson ◽

Deborah Hodgson ◽

Megan J. Oaten ◽

Luba Sominsky ◽

Mehmet Mahmut ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune Response ◽

Negative Control ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Markers ◽

Before And After ◽

Secondary Analyses ◽

Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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