Macrophage migration inhibitory factor (MIF) is critical for the host resistance against Toxoplasma gondii

被引：56

作者：

Flores, Marcos ^{[2
]}

Saavedra, Rafael ^{[3
]}

Bautista, Rocio ^{[2
]}

Viedma, Rubi ^{[2
]}

Tenorio, Eda P. ^{[3
]}

Leng, Lin ^{[4
]}

Sanchez, Yuriko ^{[2
]}

Juarez, Imelda ^{[2
]}

Satoskar, Anjali A. ^{[7
]}

Shenoy, Asha S. ^{[5
,6
]}

Terrazas, Luis I. ^{[2
]}

Bucala, Richard ^{[4
]}

Barbi, Joseph ^{[1
]}

Satoskar, Abhay R. ^{[1
]}

Rodriguez-Sosa, Miriam ^{[2
]}

机构：

[1] Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA

[2] Univ Nacl Autonoma Mexico, Unidad Biomed, FES Iztacala, Mexico City 04510, DF, Mexico

[3] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico

[4] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA

[5] Seth GS Med Coll, Dept Pathol, Bombay, Maharashtra, India

[6] King Edward Mem Hosp, Bombay, Maharashtra, India

[7] Ohio State Univ, Dept Pathol, Med Ctr, Columbus, OH 43210 USA

来源：

FASEB JOURNAL | 2008年 / 22卷 / 10期

基金：

美国国家卫生研究院;

关键词：

proinflammatory cytokines; innate immunity; cerebral toxoplasmosis;

D O I：

10.1096/fj.08-111666

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Macrophage migration inhibitory factor (MIF) exerts either a protective or a deleterious role in the immune response to different pathogens. We analyzed herein the role of MIF in the host control of toxoplasmosis using MIF-/- mice backcrossed to either the BALB/c or the C57BL/6 genetic backgrounds. Both, wild-type (WT) BALB/c and MIF-/- BALB/c mice were susceptible to infection with highly virulent RH as well as moderately virulent ME49 strains of T. gondii. MIF-/- mice, however, showed greater liver damage and more brain cysts, produced less proinflammatory cytokines, and succumbed significantly faster than WT mice. Bone marrow-derived dendritic cells (BMDCs) from MIF-/- mice produced less interleukin-1 beta, interleukin-12, and tumor necrosis factor-alpha than WT BMDCs after stimulation with soluble Toxoplasma antigen (STAB). Similar observations were made in CD11c(+) low-density cells isolated from the spleens of MIF-/- mice challenged with STAB. MIF-/- C57BL/6 mice succumbed to ME49 infection faster than their WT counterparts. C57BL/6 mice that succumbed to infection with the ME49 strain produced less MIF than resistant BALB/c mice similarly infected. Interestingly, an analysis of brains from patients with cerebral toxoplasmosis showed low levels of MIF expression. Together, these findings demonstrate that MIF plays a critical role in mediating host resistance against T. Gondii.

引用

页码：3661 / 3671

页数：11

共 56 条

[1] Regulation of the CTL response by macrophage migration inhibitory factor [J].

Abe, R ;

Peng, T ;

Sailors, J ;

Bucala, R ;

Metz, CN .

JOURNAL OF IMMUNOLOGY, 2001, 166 (02) :747-753

[2] Mechanisms of innate resistance to Toxoplasma gondii infection [J].

Alexander, J ;

SchartonKersten, TM ;

Yap, G ;

Roberts, CW ;

Liew, FY ;

Sher, A .

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES, 1997, 352 (1359) :1355-1359

[3] CCR5 provides a signal for microbial induced production of IL-12 by CD8α+ dendritic cells [J].

Aliberti, J ;

Sousa, CRE ;

Schito, M ;

Hieny, S ;

Wells, T ;

Huffnagle, GB ;

Sher, A .

NATURE IMMUNOLOGY, 2000, 1 (01) :83-87

[4] Host persistence:: Exploitation of anti-inflammatory pathways by Toxoplasma gondii [J].

Aliberti, J .

NATURE REVIEWS IMMUNOLOGY, 2005, 5 (02) :162-170

[5] An essential regulatory role for macrophage migration inhibitory factor in T-cell activation [J].

Bacher, M ;

Metz, CN ;

Calandra, T ;

Mayer, K ;

Chesney, J ;

Lohoff, M ;

Gemsa, D ;

Donnelly, T ;

Bucala, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7849-7854

[6]

Bacher M, 1997, AM J PATHOL, V150, P235

[7] Human cytomegalovirus-mediated induction of MIF in fibroblasts [J].

Bacher, M ;

Eickmann, M ;

Schrader, J ;

Gemsa, D ;

Heiske, A .

VIROLOGY, 2002, 299 (01) :32-37

[8] Immunoglobulin gene rearrangement analysis in composite Hodgkin disease and large B-cell lymphoma: Evidence for receptor revision of immunoglobulin heavy chain variable region genes in Hodgkin-Reed-Sternberg cells? [J].

Bellan, C ;

Lazzi, S ;

Zazzi, M ;

Lalinga, AV ;

Palummo, N ;

Galieni, P ;

Marafioti, T ;

Tonini, T ;

Cinti, C ;

Leoncini, L ;

Pileri, SA ;

Tosi, P .

DIAGNOSTIC MOLECULAR PATHOLOGY, 2002, 11 (01) :2-8

[9] The emerging role of MIF in septic shock and infection [J].

Bernhagen, J ;

Calandra, T ;

Bucala, R .

BIOTHERAPY, 1995, 8 (02) :123-127

[10]

Bliss SK, 1999, J IMMUNOL, V162, P7369

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