Monday, March 02, 2015

Secreted Toxoplasma gondii molecules interfere with expression of MHC-II in interferon gamma-activated macrophages

 2015 Feb 23. pii: S0020-7519(15)00024-7. doi: 10.1016/j.ijpara.2015.01.003. [Epub ahead of print]


The obligate intracellular protozoan parasite Toxoplasma gondii interferes with major histocompatibility complex (MHC)-II antigen presentation to dampen host CD4+ T cell responses. While it is known that T. gondii inhibits MHC-II gene transcription and expression in infected host cells, the mechanism of this host manipulation is unknown. Here, we show that soluble parasite proteins inhibit IFNγ-induced expression of MHC-II on the surface of the infected cell in a dose-dependent response that was abolished by protease treatment. Subcellular fractionation of T. gondii tachyzoites revealed that the MHC-II inhibitory activity co-partitioned with rhoptries (ROP) and/or dense granules (GRA). However, parasite mutants deleted for single ROP or GRA genes (ROP1, 4/7, 14, 16 and 18 or GRA 2 - 9 and 12 knock-out strains) retained the ability to inhibit expression of MHC-II. In addition, excreted/secreted antigens (ESA) released by extracellular tachyzoites displayed immunomodulatory activity characterized by an inhibition of MHC-II expression, and reduced expression and release of TNFα by macrophages. Tandem MS analysis of parasite ESA generated a list of T. gondii secreted proteins that may participate in MHC-II inhibition and the modulation of host immune functions.
Copyright © 2015. Published by Elsevier Ltd.


Antigen presentation; Excreted/secreted antigens; Immunomodulation; Major histocompatibility complex II; Secretory organelles; Toxoplasma gondii
[PubMed - as supplied by publisher] 

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