Identification of a TNF-α inducer MIC3 originating from the microneme of non-cystogenic, virulent Toxoplasma gondii

Toxoplasma gondii is an opportunistic parasite with avirulent cystogenic and highly virulent non-cystogenic isolates. Although non-cystogenic strains are considered the most virulent, there are also marked genetic and virulence differences among these strains. Excretory-secretory antigens (ESAs) of T. gondii are critical for the invasion process and the immune response of the host. To better understand the differences in virulence between non-cystogenic T. gondii isolates, we studied ESAs of the RH strain (Type I), and the very prevalent in China, but less virulent TgCtwh3 strain (Chinese 1). ESAs of RH and TgCtwh3 triggered different levels of TNF-α production and macrophage M1 polarization. Using iTRAQ analysis, 27 differentially expressed proteins originating from secretory organelles and surface were quantified. Of these proteins, 11 microneme-associated proteins (MICs), 6 rhoptry proteins, 2 dense granule proteins and 5 surface proteins were more abundant in RH than in TgCtwh3. The protein-protein correlation network was employed to identify the important functional node protein MIC3, which was upregulated 5-fold in RH compared with TgCtwh3. MIC3 was experimentally confirmed to evoke a TNF-α secretory response, and it also induced macrophage M1 polarization. This result suggests that MIC3 is a potentially useful immunomodulator that induces TNF-α secretion and macrophage M1 polarization.

Medienart:

E-Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:6

Enthalten in:

Scientific reports - 6(2016) vom: 21. Dez., Seite 39407

Sprache:

Englisch

Beteiligte Personen:

Qiu, Jingfan [VerfasserIn]
Wang, Lijuan [VerfasserIn]
Zhang, Rong [VerfasserIn]
Ge, Ke [VerfasserIn]
Guo, Hongfei [VerfasserIn]
Liu, Xinjian [VerfasserIn]
Liu, Jinfeng [VerfasserIn]
Kong, Delong [VerfasserIn]
Wang, Yong [VerfasserIn]

Links:

Volltext

Themen:

Immunologic Factors
Journal Article
MIC3 protein, Toxoplasma gondii
Membrane Proteins
Protozoan Proteins
Research Support, Non-U.S. Gov't
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 20.06.2018

Date Revised 13.11.2018

published: Electronic

Citation Status MEDLINE

doi:

10.1038/srep39407

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM267344627