Critical role for the immunoproteasome subunit LMP7 in the resistance of mice to <i>Toxoplasma gondii</i> infection

Tu, Liping; Moriya, Chikako; Imai, Takashi; Ishida, Hidekazu; Tetsutani, Kohhei; Duan, Xuefeng; Murata, Shigeo; Tanaka, Keiji; Shimokawa, Chikako; Hisaeda, Hajime; Himeno, Kunisuke

doi:10.1002/eji.200839117

Cited by 38 publications

(18 citation statements)

References 51 publications

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“…To what extent this situation has evolved to provide a viral advantage is not clear, but the extent of the impact is very evident, and appears to be a property of the viral sequence itself. These data can be added to the renewed accumulation of interest in the impact of the immunoproteasome in infection and inflammation, following studies on LCMV [28] and toxoplasma [49] (recently reviewed in Ref. [50]).…”

Section: Discussionmentioning

confidence: 99%

A Dominant Role for the Immunoproteasome in CD8+ T Cell Responses to Murine Cytomegalovirus

et al. 2011

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Murine cytomegalovirus (MCMV) is an important animal model of human cytomegalovirus (HCMV), a β-Herpesvirus that infects the majority of the world's population and causes disease in neonates and immunocompromised adults. CD8+ T cells are a major part of the immune response to MCMV and HCMV. Processing of peptides for presentation to CD8+ T cells may be critically dependent on the immunoproteasome, expression of which is affected by MCMV. However, the overall importance of the immunoproteasome in the generation of immunodominant peptides from MCMV is not known. We therefore examined the role of the immunoproteasome in stimulation of CD8+ T cell responses to MCMV – both conventional memory responses and those undergoing long-term expansion or “inflation”. We infected LMP7−/− and C57BL/6 mice with MCMV or with newly-generated recombinant vaccinia viruses (rVVs) encoding the immunodominant MCMV protein M45 in either full-length or epitope-only minigene form. We analysed CD8+ T cell responses using intracellular cytokine stain (ICS) and MHC Class I tetramer staining for a panel of MCMV-derived epitopes. We showed a critical role for immunoproteasome in MCMV affecting all epitopes studied. Interestingly we found that memory “inflating” epitopes demonstrate reduced immunoproteasome dependence compared to non-inflating epitopes. M45-specific responses induced by rVVs remain immunoproteasome-dependent. These results help to define a critical restriction point for CD8+ T cell epitopes in natural cytomegalovirus (CMV) infection and potentially in vaccine strategies against this and other viruses.

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Section: Discussionmentioning

confidence: 99%

A Dominant Role for the Immunoproteasome in CD8+ T Cell Responses to Murine Cytomegalovirus

et al. 2011

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“…75 Clearance of another parasite, Toxoplasma gondii , was also severely compromised in LMP7-deficient mice, and to a lesser degree in LMP2-deficient mice. 76 …”

Section: Immunoproteasome Functionmentioning

confidence: 99%

Immunoproteasomes

Ferrington

Gregerson

2012

Progress in Molecular Biology and Translational Science

340

217

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“…On the other hand, in a mouse model of CVB3 infection, Jäkel et al [83] observed that early type I interferon responses and concomitant upregulation of immunosubunit expression, along with other components of the MHC class I antigen processing pathway, correlated with resistance to chronic infection. LMP7-deficient mice show an enhanced suscepitibility to Toxoplasma infection [84] and, remarkably, a delayed clearance of L. monocytogenes from the liver that correlated with diminished production of an immunoproteasome-dependent epitope [48]. Thus, analyses of a large variety of infection models including different types of pathogens may lead to a readjustment of our present view, i.e.…”

Section: Effects Of Immunoproteasome Expression On Pathogen-specific mentioning

confidence: 99%

The role of the proteasome in the generation of MHC class I ligands and immune responses

Sijts

Kloetzel

2011

Cell. Mol. Life Sci.

229

150

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The ubiquitin–proteasome system (UPS) degrades intracellular proteins into peptide fragments that can be presented by major histocompatibility complex (MHC) class I molecules. While the UPS is functional in all mammalian cells, its subunit composition differs depending on cell type and stimuli received. Thus, cells of the hematopoietic lineage and cells exposed to (pro)inflammatory cytokines express three proteasome immunosubunits, which form the catalytic centers of immunoproteasomes, and the proteasome activator PA28. Cortical thymic epithelial cells express a thymus-specific proteasome subunit that induces the assembly of thymoproteasomes. We here review new developments regarding the role of these different proteasome components in MHC class I antigen processing, T cell repertoire selection and CD8 T cell responses. We further discuss recently discovered functions of proteasomes in peptide splicing, lymphocyte survival and the regulation of cytokine production and inflammatory responses.

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Critical role for the immunoproteasome subunit LMP7 in the resistance of mice to Toxoplasma gondii infection

Cited by 38 publications

References 51 publications

A Dominant Role for the Immunoproteasome in CD8+ T Cell Responses to Murine Cytomegalovirus

A Dominant Role for the Immunoproteasome in CD8+ T Cell Responses to Murine Cytomegalovirus

Immunoproteasomes

The role of the proteasome in the generation of MHC class I ligands and immune responses

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