The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

Brandenburg, Julius; Reiling, Norbert

doi:10.3389/fimmu.2016.00635

Cited by 31 publications

(27 citation statements)

References 139 publications

(164 reference statements)

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“…Increasing evidence suggests a regulatory function of Wnt proteins in inflammation, cancers, and infectious diseases. Other pathogens such www.nature.com/scientificreports www.nature.com/scientificreports/ as Mycobacterium tuberculosis, influenza, Hepatitis B virus, and certain bunyaviruses are known to manipulate the host Wnt network to enhance immune evasion and replication [68][69][70][71][72] . Specifically, we observed high expression of genes encoding the Wnt proteins, Wnt6 and Wnt5a, in fatal subjects.…”

Section: Discussionmentioning

confidence: 99%

Immune correlates of postexposure vaccine protection against Marburg virus

Woolsey

Jankeel

Matassov

et al. 2020

Sci Rep

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Postexposure immunization can prevent disease and reduce transmission following pathogen exposure. The rapid immunostimulatory properties of recombinant vesicular stomatitis virus (rVSV)-based vaccines make them suitable postexposure treatments against the filoviruses Ebola virus and Marburg virus (MARV); however, the mechanisms that drive this protection are undefined. Previously, we reported 60-75% survival of rhesus macaques treated with rVSV vectors expressing MARV glycoprotein (GP) 20-30 minutes after a low dose exposure to the most pathogenic variant of MARV, Angola. Survival in this model was linked to production of GP-specific antibodies and lower viral load. To confirm these results and potentially identify novel correlates of postexposure protection, we performed a similar experiment, but analyzed plasma cytokine levels, frequencies of immune cell subsets, and the transcriptional response to infection in peripheral blood. In surviving macaques (80-89%), we observed induction of genes mapping to antiviral and interferon-related pathways early after treatment and a higher percentage of T helper 1 (Th1) and NK cells. In contrast, the response of non-surviving macaques was characterized by hypercytokinemia; a T helper 2 signature; recruitment of low HLA-DR expressing monocytes and regulatory T-cells; and transcription of immune checkpoint (e.g., PD-1, LAG3) genes. These results suggest dysregulated immunoregulation is associated with poor prognosis, whereas early innate signaling and Th1-skewed immunity are important for survival. Members of the genera Marburgvirus (MARV) and Ebolavirus (EBOV) are pathogens in the family Filoviridae that cause a similar life-threatening hemorrhagic disease in humans and non-human primates (NHPs) 1. More than 30,000 people have been infected with EBOV, whereas 469 cumulative cases and 376 recorded deaths are attributed to Marburg virus disease (MVD) 2-4. Although fewer cases are recorded for MARV, future outbreaks and spread of the virus into non-endemic regions are of great concern. MVD has an overall mortality rate of 81% and imported cases have occurred in Germany, the former Yugoslavia (presently Serbia), the Netherlands, and the United States 1-4. Moreover, the Egyptian fruit bat host reservoir has a wide geographic distribution 5. While MARV is thought to be limited to equatorial Africa, a research group that surveyed a large South African bat colony found that ~53% of these animals were seropositive for the virus, and recently MARV was isolated from bats in West Africa for the first time 6,7. Surveillance in the latter region also revealed serological evidence of filoviruses (MARV and EBOV) circulating in human subjects prior to the 2013-2016 EBOV outbreak 8,9. The likelihood of spillover events and spread into human populations emphasizes the need for adequate countermeasures against this deadly virus. One of the most promising vaccine candidates against MARV and EBOV uses a live, attenuated recombinant vesicular stomatitis virus (rVSV) platform to express filovirus ...

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Section: Discussionmentioning

confidence: 99%

Immune correlates of postexposure vaccine protection against Marburg virus

Woolsey

Jankeel

Matassov

et al. 2020

Sci Rep

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“…Two main branches of classical WNT signaling cascades have been demonstrated: b-catenin-dependent (canonical) and b-catenin-independent (noncanonical) WNT signaling, the use of which depends on the context (19,20). Many studies indicated that WNT5A exerts proinflammatory functions on various types of immune and nonimmune cells, thus playing key roles in tissue homeostasis and modulation of immune responses in pathology (21,22). WNT5A not only contributes to maintain IFN levels in macrophages but also supports macrophage survival (20).…”

Section: Il-36g Promotes Killing Of Mycobacterium Tuberculosis By Macmentioning

confidence: 99%

IL-36γ Promotes Killing of Mycobacterium tuberculosis by Macrophages via WNT5A-Induced Noncanonical WNT Signaling

Gao

Wen

et al. 2019

The Journal of Immunology

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Mycobacterium tuberculosis, which primarily infects mononuclear phagocytes, remains the leading bacterial cause of enormous morbidity and mortality because of bacterial infections in humans throughout the world. The IL-1 family of cytokines is critical for host resistance to M. tuberculosis. As a newly discovered subgroup of the IL-1 family, although IL-36 cytokines have been proven to play roles in protection against M. tuberculosis infection, the antibacterial mechanisms are poorly understood. In this study, we demonstrated that IL-36γ conferred to human monocyte-derived macrophages bacterial resistance through activation of autophagy as well as induction of WNT5A, a reported downstream effector of IL-1 involved in several inflammatory diseases. Further studies showed that WNT5A could enhance autophagy of monocyte-derived macrophages by inducing cyclooxygenase-2 (COX-2) expression and in turn decrease phosphorylation of AKT/mTOR via noncanonical WNT signaling. Consistently, the underlying molecular mechanisms of IL-36γ function are also mediated by the COX-2/AKT/mTOR signaling axis. Altogether, our findings reveal a novel activity for IL-36γ as an inducer of autophagy, which represents a critical inflammatory cytokine that control the outcome of M. tuberculosis infection in human macrophages.

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“…Wnt5a wird bei Infektions-und Entzündungserkrankungen, wie Tuberkulose, Sepsis, Psoriasis, rheumatoider Arthritis und Atherosklerose, induziert [35]. Die β-Catenin-abhängige Wnt-Signalisierung verstärkt somit die Entzündungsreaktion [36].…”

Section: Stadien Der Hautregenerationunclassified

Wnt-Signalwege bei kutaner Wundheilung

Houschyar

Tapking

Puladi

et al. 2019

Handchir Mikrochir plast Chir

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ZusammenfassungDie menschliche Haut ist eine effiziente Barriere, die den Organismus vor Noxen schützt. Wunden zerstören diese Barriere. Die Wundheilung ist eine in Phasen ablaufende physiologische Regeneration des zerstörten Gewebes, die im Idealfall zum Verschluss einer Wunde, insbesondere durch Neubildung von Bindegewebe und Kapillaren, führt. Der Wnt-Signalweg ist eine im gesamten Tierreich stark konservierte Signaltransduktionskaskade, durch die grundlegende zelluläre Interaktionen in multizellulären Organismen gesteuert werden. Entsprechend werden durch den Wnt-Signalweg viele Prozesse, z. B. die Balance zwischen Proliferation und Differenzierung oder die Apoptose, koordiniert. Die Wnt-Signalisierung wird durch eine Wunde aktiviert und nimmt an jeder nachfolgenden Phase des Heilungsprozesses teil, beginnend mit der Entzündungskontrolle und des programmierten Zelltods bis zur Mobilisation von Stammzellen innerhalb der Wunde. Die endogene Wnt-Signalverstärkung stellt einen attraktiven therapeutischen Ansatz dar, um die Wiederherstellung von Hautwunden zu unterstützen, da die komplexen Mechanismen des Wnt-Signalwegs im Laufe der Jahre zunehmend verstanden wurden. In dieser Übersichtsarbeit werden die aktuellen Daten zusammengefasst, um die Rolle der Wnt-Signalgebung beim Wundheilungsprozess der Haut zu verdeutlichen.

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The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

Cited by 31 publications

References 139 publications

Immune correlates of postexposure vaccine protection against Marburg virus

Immune correlates of postexposure vaccine protection against Marburg virus

IL-36γ Promotes Killing of Mycobacterium tuberculosis by Macrophages via WNT5A-Induced Noncanonical WNT Signaling

Wnt-Signalwege bei kutaner Wundheilung

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The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

Cited by 31 publications

References 139 publications

Immune correlates of postexposure vaccine protection against Marburg virus

Immune correlates of postexposure vaccine protection against Marburg virus

IL-36γ Promotes Killing of Mycobacterium tuberculosis by Macrophages via WNT5A-Induced Noncanonical WNT Signaling

﻿Wnt-Signalwege bei kutaner Wundheilung

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Wnt-Signalwege bei kutaner Wundheilung