Migration-inhibitory Factor Gene-deficient Mice Are Susceptible to Cutaneous Leishmania Major Infection

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2001 Feb 13

PMID 11159984

Citations 46

Authors

A R Satoskar

M BOZZA

M Rodriguez Sosa

G Lin

J R David

Affiliations

Soon will be listed here.

Abstract

To determine the role of endogenous migration-inhibitory factor (MIF) in the development of protective immunity against cutaneous leishmaniasis, we analyzed the course of cutaneous Leishmania major infection in MIF gene-deficient mice (MIF(-/-)) and wild-type (MIF(+/+)) mice. Following cutaneous L. major infection, MIF(-/-) mice were susceptible to disease and developed significantly larger lesions and greater parasite burdens than MIF(+/+) mice. Interestingly, antigen-stimulated lymph node cells from MIF(-/-) mice produced more interleukin-4 (IL-4) and gamma interferon (IFN-gamma) than those from MIF(+/+) mice, although the differences were statistically not significant. IFN-gamma-activated resting peritoneal macrophages from MIF(-/-) mice showed impaired macrophage leishmanicidal activity and produced significantly lower levels of nitric oxide and superoxide in vitro. The macrophages from MIF(-/-) mice, however, produced much more IL-6 than macrophages from wild-type mice. These findings demonstrate that endogenous MIF plays an important role in the development of protective immunity against L. major in vivo. Furthermore, they indicate that the susceptibility of MIF(-/-) mice to L. major infection is due to impaired macrophage leishmanicidal activity rather than dysregulation of Th1 and Th2 responses.

Citing Articles

The Role of Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (D-DT/MIF-2) in Infections: A Clinical Perspective.

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Host M-CSF induced gene expression drives changes in susceptible and resistant mice-derived BMdMs upon infection.

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Cytokines and Signaling Networks Regulating Disease Outcomes in Leishmaniasis.

Saha A, Roy S, Ukil A Infect Immun. 2022; 90(8):e0024822.

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The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm.

Stijlemans B, Schoovaerts M, De Baetselier P, Magez S, De Trez C Front Immunol. 2022; 13:865395.

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Role of Host and Parasite MIF Cytokines during Infection.

Holowka T, Bucala R Trop Med Infect Dis. 2020; 5(1).

PMID: 32244916 PMC: 7157535. DOI: 10.3390/tropicalmed5010046.

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