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Special Issue "Toxins and Immunology"

A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: closed (31 December 2018)

Special Issue Editor

Guest Editor
Prof. Jean Marc Cavaillon

Laboratory of Human Histopathology and Animal Models, Institut Pasteur, 28, rue du Dr Roux, 75015 Paris, France
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Special Issue Information

Dear Colleauges,

Toxinology and immunology have been closely linked since their respective births, when Behring and Kitasato demonstrated that serotherapy was effective against diphtheria, when Roux and Yersin discovered its dreadful toxin, and when Ramon described the anatoxin that allowed the elaboration of an effective vaccine, and discovered the use of adjuvant to boost the antibody response. Toxins are part of the bacterial arsenal and are responsible for danger of venoms. As a consequence, they need to be targeted by the immune system. Elaboration of neutralizing specific antibodies is part of the immune defense, and the use of serotherapy remains of great help in the case of venom poisoning. Some toxins behave as superantigens and trigger immune cells in a very specific fashion. Toxins activate the inflammasome and the elaboration of endogenous pyrogens that cause fever, a protective mechanism against infection. However, toxins can also induce a cytokine storm with their pathophysiological consequences. Their toxicity can be directed against the immune leukocytes, weakening the immune defense. However, scientists have also diverted its main property to use it as a weapon against tumor cells. Finally, the existence of IgE against toxins may explain their maintenance through evolution despite their side effect in allergy.

The aim of this Special Issue is to offer an overview of the current knowledge in the interaction between toxins and the immune system.

Prof. Jean Marc Cavaillon
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antibodies
  • Cancer
  • Cell death
  • Fever
  • IgE
  • Inflammation
  • Innate immunity
  • Leukocytes
  • Serotherapy
  • Superantigens.

Published Papers (5 papers)

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Research

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Open AccessArticle Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo
Received: 24 November 2018 / Revised: 9 January 2019 / Accepted: 9 January 2019 / Published: 14 January 2019
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Abstract
Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty [...] Read more.
Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 µg crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-α, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5–0.6 OD/mg) and MPO (0.1–0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 μg crotamine resulted in serum NO (64.7 μM) and local tissue NO (58.5 μM) levels higher or equivalent to those recorded for their respective histamine controls (55.7 μM and 59.0 μM). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4–45.8 mg/mL), which was significantly greater than control values. Crotamine (400 μg) also caused an increase in serum TNF-α, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0–1.8 μM/mL) and decrease in SH levels (124.7–19.5 μM/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form. Full article
(This article belongs to the Special Issue Toxins and Immunology)
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Open AccessArticle SS1P Immunotoxin Induces Markers of Immunogenic Cell Death and Enhances the Effect of the CTLA-4 Blockade in AE17M Mouse Mesothelioma Tumors
Toxins 2018, 10(11), 470; https://doi.org/10.3390/toxins10110470
Received: 16 October 2018 / Revised: 5 November 2018 / Accepted: 8 November 2018 / Published: 14 November 2018
Cited by 1 | PDF Full-text (1218 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
SS1P is an anti-mesothelin immunotoxin composed of a targeting antibody fragment genetically fused to a truncated fragment of Pseudomonas exotoxin A. Delayed responses reported in mesothelioma patients receiving SS1P suggest that anti-tumor immunity is induced. The goal of this study is to evaluate [...] Read more.
SS1P is an anti-mesothelin immunotoxin composed of a targeting antibody fragment genetically fused to a truncated fragment of Pseudomonas exotoxin A. Delayed responses reported in mesothelioma patients receiving SS1P suggest that anti-tumor immunity is induced. The goal of this study is to evaluate if SS1P therapy renders mesothelioma tumors more sensitive to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint blockade. We evaluated the ability of SS1P to induce adenosine triphosphate (ATP) secretion and calreticulin expression on the surface of AE17M mouse mesothelioma cells. Both properties are associated with immunogenic cell death. Furthermore, we treated these tumors with intra-tumoral SS1P and systemic CTLA-4. We found that SS1P increased the release of ATP from AE17M cells in a dose and time-dependent manner. In addition, SS1P induced calreticulin expression on the surface of AE17M cells. These results suggest that SS1P promotes immunogenic cell death and could sensitize tumors to anti-CTLA-4 based therapy. In mouse studies, we found that the combination of anti-CTLA-4 with intra-tumoral SS1P induced complete regressions in most mice and provided a statistically significant survival benefit compared to monotherapy. The surviving mice were protected from tumor re-challenge, indicating the development of anti-tumor immunity. These findings support the use of intra-tumoral SS1P in combination with anti-CTLA-4. Full article
(This article belongs to the Special Issue Toxins and Immunology)
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Review

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Open AccessReview Serotherapy against Voltage-Gated Sodium Channel-Targeting α-Toxins from Androctonus Scorpion Venom
Received: 23 November 2018 / Revised: 18 January 2019 / Accepted: 21 January 2019 / Published: 23 January 2019
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Abstract
Because of their venom lethality towards mammals, scorpions of the Androctonus genus are considered a critical threat to human health in North Africa. Several decades of exploration have led to a comprehensive inventory of their venom components at chemical, pharmacological, and immunological levels. [...] Read more.
Because of their venom lethality towards mammals, scorpions of the Androctonus genus are considered a critical threat to human health in North Africa. Several decades of exploration have led to a comprehensive inventory of their venom components at chemical, pharmacological, and immunological levels. Typically, these venoms contain selective and high affinity ligands for the voltage-gated sodium (Nav) and potassium (Kv) channels that dictate cellular excitability. In the well-studied Androctonus australis and Androctonus mauretanicus venoms, almost all the lethality in mammals is due to the so-called α-toxins. These peptides commonly delay the fast inactivation process of Nav channels, which leads to increased sodium entry and a subsequent cell membrane depolarization. Markedly, their neutralization by specific antisera has been shown to completely inhibit the venom’s lethal activity, because they are not only the most abundant venom peptide but also the most fatal. However, the structural and antigenic polymorphisms in the α-toxin family pose challenges to the design of efficient serotherapies. In this review, we discuss past and present accomplishments to improve serotherapy against Androctonus scorpion stings. Full article
(This article belongs to the Special Issue Toxins and Immunology)
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Open AccessReview Pseudomonas Exotoxin Immunotoxins and Anti-Tumor Immunity: From Observations at the Patient’s Bedside to Evaluation in Preclinical Models
Received: 11 December 2018 / Revised: 4 January 2019 / Accepted: 4 January 2019 / Published: 5 January 2019
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Abstract
Immunotoxins are protein drugs composed of a targeting domain genetically fused to a protein toxin. One killing domain being explored is a truncated Pseudomonas exotoxin A (PE). PE based immunotoxins are designed to kill cells directly by inhibiting their ability to synthesize proteins. [...] Read more.
Immunotoxins are protein drugs composed of a targeting domain genetically fused to a protein toxin. One killing domain being explored is a truncated Pseudomonas exotoxin A (PE). PE based immunotoxins are designed to kill cells directly by inhibiting their ability to synthesize proteins. However, observations from clinical trials suggest that this alone cannot explain their anti-tumor activity. Here we discuss patterns of clinical responses suggesting that PE immunotoxins can provoke anti-tumor immunity, and review murine models that further support this ability. In addition, we describe our preclinical effort to develop a combination therapy of local PE immunotoxins with a systemic anti-CTLA-4 immune check point blocking antibody. The combination eradicated murine tumors and prolonged the survival of mice. Clinical trials that test the ability of immunotoxins to augment immunotherapy have been recently opened. Full article
(This article belongs to the Special Issue Toxins and Immunology)
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Open AccessReview Interaction between Insects, Toxins, and Bacteria: Have We Been Wrong So Far?
Received: 8 June 2018 / Revised: 1 July 2018 / Accepted: 2 July 2018 / Published: 6 July 2018
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Abstract
Toxins are a major virulence factor produced by many pathogenic bacteria. In vertebrates, the response of hosts to the bacteria is inseparable from the response to the toxins, allowing a comprehensive understanding of this tripartite host-pathogen-toxin interaction. However, in invertebrates, this interaction has [...] Read more.
Toxins are a major virulence factor produced by many pathogenic bacteria. In vertebrates, the response of hosts to the bacteria is inseparable from the response to the toxins, allowing a comprehensive understanding of this tripartite host-pathogen-toxin interaction. However, in invertebrates, this interaction has been investigated by two complementary but historically distinct fields of research: toxinology and immunology. In this article, I highlight how such dichotomy between these two fields led to a biased, or even erroneous view of the ecology and evolution of the interaction between insects, toxins, and bacteria. I focus on the reason behind such a dichotomy, on how to bridge the fields together, and on confounding effects that could bias the outcome of the experiments. Finally, I raise four questions at the border of the two fields on the cross-effects between toxins, bacteria, and spores that have been largely underexplored to promote a more comprehensive view of this interaction. Full article
(This article belongs to the Special Issue Toxins and Immunology)
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Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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