The plasma membrane-associated Ca2+- binding protein PCaP1 is required for oligogalacturonide and flagellin-induced priming and immunity

Early signaling events in response to elicitation include reversible protein phosphorylation and re-localization of plasma membrane (PM) proteins. Oligogalacturonides (OGs) are a class of Damage-Associated Molecular Patterns (DAMPs) that act as endogenous signals to activate the plant immune response. Previous data on early phosphoproteome changes in Arabidopsis thaliana upon OG perception uncovered the immune-related phospho-regulation of several membrane proteins, among which PCaP1, a PM-anchored protein with actin filament-severing activity, was chosen for its potential involvement in OG- as well as flagellin-triggered responses. Here we demonstrate that PCaP1 is required for late, but not early, responses induced by OGs and flagellin. Moreover, pcap1 mutants, unlike the wild type, are impaired in the recovery of full responsiveness to a second treatment with OGs performed 24 h after the first one. Localization studies on PCaP1 upon OG treatment in plants expressing a functional PCaP1-GFP fusion under the control of PCaP1 promoter revealed fluorescence on the PM, organized in densely packed punctate structures, previously reported as microdomains. Fluorescence was found to be associated also with endocytic vesicles, the number of which rapidly increased after OG treatment, suggesting both an endocytic turnover of PCaP1 for maintaining its homeostasis at the PM and an OG-induced endocytosis.

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TLR4 regulates rabies virus-induced humoral immunity through recruitment of cDC2 to lymph organs

Journal of Virology ◽

10.1128/jvi.00829-21 ◽

2021 ◽

Author(s):

Chen Chen ◽

Chengguang Zhang ◽

Haoqi Li ◽

Zongmei Wang ◽

Yueming Yuan ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Rabies Virus ◽

Humoral Immunity ◽

Humoral Immune Response ◽

Critical Role ◽

Wild Type ◽

Humoral Immune ◽

Specific Igg ◽

Molecular Patterns

Rabies, caused by rabies virus (RABV), is fatal to both humans and animals around the world. Effective clinical therapy for rabies has not been achieved, and vaccination is the most effective means of preventing and controlling rabies. Although different vaccines, such as live attenuated and inactivated vaccines, can induce different immune responses, different expression of pattern recognition receptors (PRRs) also causes diverse immune responses. Toll-like receptor 4 (TLR4) is a pivotal PRR that induces cytokine production and bridges innate and adaptive immunity. Importantly, TLR4 recognizes various virus-derived pathogen-associated molecular patterns (PAMPs) and virus-induced damage-associated molecular patterns (DAMPs), usually leading to the activation of immune cells. However, the role of TLR4 in the humoral immune response induced by RABV has not been revealed yet. Based on TLR4-deficient ( TLR4 -/- ) and wild-type (WT) mouse models, we report that TLR4-dependent recruitment of the conventional type-2 dendritic cells (CD8α - CD11b + cDC2) into secondary lymph organs (SLOs) is critical for antigen presentation. cDC2-initiated differentiation of Tfh cells promotes the proliferation of germinal centre (GC) B cells, the formation of GCs, and the production of plasma cells (PCs), all of which contribute to the production of RABV-specific IgG and virus-neutralizing antibodies (VNAs). Collectively, our work demonstrates that TLR4 is necessary for the recruitment of cDC2 and for the induction of RABV-induced humoral immunity, which is regulated by the cDC2-Tfh-GC B axis. IMPORTANCE Vaccination is the most efficient method to prevent rabies. TLR4, a well-known immune sensor, plays a critical role in initiating innate immune response. Here, we found that TLR4 deficiency ( TLR4 -/- ) mice suppressed the induction of humoral immune response after immunization with rabies virus (RABV), including reduced production of VNAs and RABV-specific IgG, compared with that occurred in wild-type (WT) mice. As a consequence, TLR4 -/- mice exhibited higher mortality than WT mice after challenge with virulent RABV. Importantly, further investigation found that TLR4 signaling promoted the recruitment of cDC2 (CD8α + CD11b - ), a subset of cDCs known to induce CD4 + T cell immunity through their MHC-II presentation machinery. Our results imply that TLR4 is indispensable for an efficient humoral response to rabies vaccine, which provides new insight into the development of novel rabies vaccines.

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2. First responders: the innate immune response

The Immune System: A Very Short Introduction ◽

10.1093/actrade/9780198753902.003.0002 ◽

2017 ◽

pp. 17-29

Author(s):

Paul Klenerman

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Acute Phase Response ◽

First Responders ◽

Fundamental Question ◽

Innate Immune ◽

Rapid Action ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

How does the immune system know when to respond? ‘First responders: the innate immune response’ considers this fundamental question that is central to understanding both normal (e.g. to infections) and abnormal (e.g. in auto-immune diseases) responses; and designing vaccines and new therapies in cancer and infectious diseases. It looks at how ‘danger’ is sensed by the immune system through pathogen-associated molecular patterns and damage-associated molecular patterns. Having been alerted, it is important that rapid action is taken to limit the spread of a pathogen. A number of responses can be initiated immediately, forming a critical part of our innate immunity, which are followed by the acute phase response.

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Purinergic signaling, DAMPs, and inflammation

AJP Cell Physiology ◽

10.1152/ajpcell.00053.2020 ◽

2020 ◽

Vol 318 (5) ◽

pp. C832-C835 ◽

Cited By ~ 10

Author(s):

Francesco Di Virgilio ◽

Alba Clara Sarti ◽

Robson Coutinho-Silva

Keyword(s):

Plasma Membrane ◽

Purinergic Receptors ◽

Purinergic Signaling ◽

Extracellular Atp ◽

Main Metabolite ◽

P2 Purinergic Receptors ◽

Evolutionary Features ◽

Multicellular Organisms ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Danger sensing is one of the most fundamental evolutionary features enabling multicellular organisms to perceive potential threats, escape from risky situations, fight actual intruders, and repair damage. Several endogenous molecules are used to “signal damage,” currently referred to as “alarmins” or “damage-associated molecular patterns” (DAMPs), most being already present within all cells (preformed DAMPs), and thus ready to be released, and others neosynthesized following injury. Over recent years it has become overwhelmingly clear that adenosine 5′-triphosphate (ATP) is a ubiquitous and extremely efficient DAMP (thus promoting inflammation), and its main metabolite, adenosine, is a strong immunosuppressant (thus dampening inflammation). Extracellular ATP ligates and activates the P2 purinergic receptors (P2Rs) and is then degraded by soluble and plasma membrane ecto-nucleotidases to generate adenosine acting at P1 purinergic receptors (P1Rs). Extracellular ATP, P2Rs, ecto-nucleotidases, adenosine, and P1Rs are basic elements of the purinergic signaling network and fundamental pillars of inflammation.

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Reversible protein phosphorylation regulates jasmonic acid‐dependent and ‐independent wound signal transduction pathways in Arabidopsis thaliana

The Plant Journal ◽

10.1046/j.1365-313x.1998.00020.x ◽

1998 ◽

Vol 13 (2) ◽

pp. 153-165 ◽

Cited By ~ 91

Author(s):

Enrique Rojo ◽

Elena Titarenko ◽

José León ◽

Susanne Berger ◽

Guy Vancanneyt ◽

...

Keyword(s):

Signal Transduction ◽

Arabidopsis Thaliana ◽

Jasmonic Acid ◽

Protein Phosphorylation ◽

Signal Transduction Pathways ◽

Wound Signal ◽

Reversible Protein Phosphorylation

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Electrophoretic analysis of plasma membrane proteins of wild-type and differentiation-deficient mutant strains ofPodospora anserina

Current Microbiology ◽

10.1007/bf01567285 ◽

1983 ◽

Vol 9 (3) ◽

pp. 133-139 ◽

Cited By ~ 2

Author(s):

Marc Bonneu ◽

Jacques Labarère

Keyword(s):

Plasma Membrane ◽

Membrane Proteins ◽

Electrophoretic Analysis ◽

Deficient Mutant ◽

Wild Type ◽

Plasma Membrane Proteins ◽

Mutant Strains

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Methylation of aquaporins in plant plasma membrane

Biochemical Journal ◽

10.1042/bj20060569 ◽

2006 ◽

Vol 400 (1) ◽

pp. 189-197 ◽

Cited By ~ 51

Author(s):

Véronique Santoni ◽

Lionel Verdoucq ◽

Nicolas Sommerer ◽

Joëlle Vinh ◽

Delphine Pflieger ◽

...

Keyword(s):

Plasma Membrane ◽

Membrane Proteins ◽

Water Permeability ◽

Plant Root ◽

Ectopic Expression ◽

Regulatory Mechanisms ◽

Wild Type ◽

Post Translational Modification ◽

Suspension Cells ◽

Plant Plasma Membrane

A thorough analysis, using MS, of aquaporins expressed in plant root PM (plasma membrane) was performed, with the objective of revealing novel post-translational regulations. Here we show that the N-terminal tail of PIP (PM intrinsic protein) aquaporins can exhibit multiple modifications and is differentially processed between members of the PIP1 and PIP2 subclasses. Thus the initiating methionine was acetylated or cleaved in native PIP1 and PIP2 isoforms respectively. In addition, several residues were detected to be methylated in PIP2 aquaporins. Lys3 and Glu6 of PIP2;1, one of the most abundant aquaporins in the PM, occurred as di- and mono-methylated residues respectively. Ectopic expression in Arabidopsis suspension cells of PIP2;1, either wild-type or with altered methylation sites, revealed an interplay between methylation at the two sites. Measurements of water transport in PM vesicles purified from these cells suggested that PIP2;1 methylation does not interfere with the aquaporin intrinsic water permeability. In conclusion, the present study identifies methylation as a novel post-translational modification of aquaporins, and even plant membrane proteins, and may represent a critical advance towards the identification of new regulatory mechanisms of membrane transport.

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Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320999200831224302 ◽

2020 ◽

Vol 20 ◽

Author(s):

Thea Magrone ◽

Manrico Magrone ◽

Matteo Antonio Russo ◽

Emilio Jirillo

Keyword(s):

Immune Response ◽

Plant Defense ◽

Defense Mechanisms ◽

Systemic Acquired Resistance ◽

Plant Immunity ◽

Acquired Resistance ◽

Early Response ◽

Protein Receptors ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Background: Despite the evidence that plants do not possess sessile cells, they are able to mount a vigorous immune response against invaders or under stressful conditions. Mechanisms of action: Plants are endowed with pattern recognition receptors (PPRs) which perceive damage-associated molecular patterns and microbe-associated molecular patterns or pathogen-associated molecular patterns (PAMPs), respectively. PPR activation leads to either the initiation of PAMP-triggered immunity (PTI) (early response) or the effectortriggered immunity (ETI). Both PTI and ETI contribute to plant systemic acquired resistance as also an expression of immunological memory or trained immunity. Plant immune receptors: PTI is initiated by activation of both receptor-like kinases and receptor-like proteins, while ETI depends on nucleotide-binding leucine-rich-repeat protein receptors for microbe recognition. Peptides involved in plant defenses: Plant chloroplasts contribute to both PTI and ETI through production of peptides which act as hormones or phytocytokines. Salicylic acid, jasmonic acid and ethylene are the major compounds involved in plant defense. Specific aims: The interaction between plant receptors and/or their products and bacterial components will be discussed. Also emphasis will be placed on plant microbiome for its contribution to plant immune response. Finally, the mutual interplay between insects and plants will also be illustrated. Conclusion: A better knowledge on plant immunity may pave the way for the exploitation of plant derivatives in the field of agriculture and medicine, as well.

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SARM1mediates TLR9-induced vascular hyperpermeability following hemorrhagic shock

American Journal of BioMedicine ◽

10.18081/2333-5106/015-10/644-657 ◽

2018 ◽

Vol 6 (3) ◽

pp. 264-279

Author(s):

Morrison R. Doelle ◽

Benjamin M. Predmore

Keyword(s):

Hemorrhagic Shock ◽

Causes Of Death ◽

Multiple Organ ◽

In Vivo Model ◽

Wild Type ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns ◽

Significant Health ◽

Necrosis Factor

Hemorrhagic shock (HS) result in multiple organ dysfunction syndrome (MODS) and inflammatory response. It is one of the world's leading causes of death within the first 40 years of life and thus a significant health problem. The exact mechanism is not clear. TLRs are stimulated both by pathogen-associated molecular patterns as well as by damage-associated molecular patterns, including trauma and hemorrhagic shock. In the present study, we investigated whether the SARM1 responsible for mediats-TLR9-induces inflammatory process and vascular hyperpermeability following hemorrhagic shock. Here we produced an in vivo model of severe hemorrhagic shock in adult wild type mice (40 ± 2 mmHg for 90 min, fluid resuscitation for 30 min) was employed. Mesenteric postcapillary venules were examined for changes in hyperpermeability by intravital microscopy. Blood samples were collected for measurement of tumor necrosis factor (TNF) using ELISA. Biopsies were obtained from organs for light microscopic examination. Our data suggest that SARM1 promising a new mechanisim of TLR9 involved in regulation of hemorrhagic shock and therapeutic target for the treatment of hemorrhagic shock.

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Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

Mediators of Inflammation ◽

10.1155/2020/7527953 ◽

2020 ◽

Vol 2020 ◽

pp. 1-25 ◽

Cited By ~ 11

Author(s):

Sebastiano Cicco ◽

Gerolamo Cicco ◽

Vito Racanelli ◽

Angelo Vacca

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Targeted Therapy ◽

High Mobility ◽

Neutrophil Extracellular Traps ◽

Lung Cells ◽

Extracellular Traps ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns ◽

Excessive Inflammatory Response

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.

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