Role of major histocompatibility complex II antigen‐presentation pathway genes in orange‐spotted grouper infected with Cryptocaryon irritans

2020 ◽  
Vol 43 (12) ◽  
pp. 1541-1552
Author(s):  
Jun‐Jin Deng ◽  
Shun Xu ◽  
Yan‐Wei Li ◽  
Dong‐Dong Xu ◽  
Ze‐Quan Mo ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Major Histocompatibility ◽  
Complex Ii ◽  
Cryptocaryon Irritans ◽  
Histocompatibility Complex ◽  
Antigen Presentation Pathway ◽  
Presentation Pathway ◽  
Major Histocompatibility Complex Ii

scholarly journals Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma gondii Infection

2015 ◽  
Vol 83 (10) ◽  
pp. 3865-3880 ◽  
Author(s):  
Louis-Philippe Leroux ◽  
Manami Nishi ◽  
Sandy El-Hage ◽  
Barbara A. Fox ◽  
David J. Bzik ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Invariant Chain ◽  
Complex Class ◽  
Content Type ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Antigen Presentation Pathway ◽  
Presentation Pathway ◽  
Genetic Deletion

Toxoplasma gondiiis an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known thatT. gondiiinterferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4+T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes byT. gondiiwas previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, namely, the MHC-II-associated invariant chain (Ii or CD74) and the peptide editor H2-DM, in professional antigen-presenting cells (pAPCs). Genetic deletion of CD74 restored the ability of infected dendritic cells to present a parasite antigen in the context of MHC-IIin vitro. CD74 mRNA and protein levels were, surprisingly, elevated in infected cells, whereas MHC-II and H2-DM expression was inhibited. CD74 accumulated mainly in the endoplasmic reticulum (ER), and this phenotype required live parasites, but not active replication. Finally, we compared the impacts of genetic deletion of CD74 and H2-DM genes on parasite dissemination toward lymphoid organs in mice, as well as activation of CD4+T cells and interferon gamma (IFN-γ) levels during acute infection. Cyst burdens and survival during the chronic phase of infection were also evaluated in wild-type and knockout mice. These results highlight the fact that the infection is influenced by multiple levels of parasite manipulation of the MHC-II antigen presentation pathway.

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