edoc

Interferon-γ is a crucial activator of early host immune defense against Mycobacterium ulcerans infection in mice

Bieri, Raphael and Bolz, Miriam and Ruf, Marie-Thérèse and Pluschke, Gerd. (2016) Interferon-γ is a crucial activator of early host immune defense against Mycobacterium ulcerans infection in mice. PLoS neglected tropical diseases, 10 (2). e0004450.

[img] PDF - Published Version
Available under License CC BY (Attribution).

6Mb

Official URL: http://edoc.unibas.ch/42131/

Downloads: Statistics Overview

Abstract

Buruli ulcer (BU), caused by infection with Mycobacterium ulcerans, is a chronic necrotizing human skin disease associated with the production of the cytotoxic macrolide exotoxin mycolactone. Despite extensive research, the type of immune responses elicited against this pathogen and the effector functions conferring protection against BU are not yet fully understood. While histopathological analyses of advanced BU lesions have demonstrated a mainly extracellular localization of the toxin producing acid fast bacilli, there is growing evidence for an early intra-macrophage growth phase of M. ulcerans. This has led us to investigate whether interferon-γ might play an important role in containing M. ulcerans infections. In an experimental Buruli ulcer mouse model we found that interferon-γ is indeed a critical regulator of early host immune defense against M. ulcerans infections. Interferon-γ knockout mice displayed a faster progression of the infection compared to wild-type mice. This accelerated progression was reflected in faster and more extensive tissue necrosis and oedema formation, as well as in a significantly higher bacterial burden after five weeks of infection, indicating that mice lacking interferon-γ have a reduced capacity to kill intracellular bacilli during the early intra-macrophage growth phase of M. ulcerans. This data demonstrates a prominent role of interferon-γ in early defense against M. ulcerans infection and supports the view that concepts for vaccine development against tuberculosis may also be valid for BU.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Molecular Immunology (Pluschke)
UniBasel Contributors:Bieri, Raphael and Bolz, Miriam and Ruf, Marie-Thérèse and Pluschke, Gerd
Item Type:Article, refereed
Publisher:Public Library of Science
ISSN:1935-2727
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:25 Aug 2016 10:23
Deposited On:28 Apr 2016 08:09

Repository Staff Only: item control page