Spontaneous Recovery of Pathogenicity by Leishmania Major Hsp100-/- Alters the Immune Response in Mice

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2006 Oct 24

PMID 17057085

Citations 10

Authors

Linda Reiling

Thomas Jacobs

Manfred Kroemer

Iris Gaworski

Sebastian Graefe

Joachim Clos

Affiliations

Soon will be listed here.

Abstract

By using repeated mouse infection cycles, we obtained an escape variant with restored infectivity and pathogenicity that originated from a single, noninfectious hsp100-/- gene (formerly known as DeltaclpB) replacement clone of Leishmania major, the causative agent of cutaneous leishmaniasis. This isolate elicited increased infiltration of immune cells to the site of infection and altered the polarization of the immune response in BALB/c mice from a predominantly TH2 type to a TH1 type. A clonal analysis resulted in isolation of two clones with antagonistic properties. While one clone exhibited restored infectivity in isolated macrophages but caused no persistent infection in the mouse model, the second clone was unable to infect macrophages in vitro but could establish a lasting infection and form progressive lesions in BALB/c mice. Our results add to the evidence that the TH1-TH2 dichotomy of the early immune response against L. major not only depends on the genetic predisposition of the host but also depends on intrinsic properties of the parasite.

Citing Articles

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Artemisinin-resistant Leishmania parasite modulates host cell defense mechanism and exhibits altered expression of unfolded protein response genes.

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A versatile qPCR assay to quantify trypanosomatidic infections of host cells and tissues.

Bifeld E, Nevado P, Bartsch J, Eick J, Clos J Med Microbiol Immunol. 2016; 205(5):449-58.

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Molecular Chaperones of Leishmania: Central Players in Many Stress-Related and -Unrelated Physiological Processes.

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