Toxoplasma gondii GRA7-Targeted ASC and PLD1 Promote Antibacterial HostDefense via PKC alpha

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486377.do
DOI
10.1371/journal.ppat.1006126
Title
Toxoplasma gondii GRA7-Targeted ASC and PLD1 Promote Antibacterial HostDefense via PKC alpha
Description
This work was supported by the National Research Foundation of Korea(NRF) grants funded by the Korea government (MSIP) the Ministry ofScience, ICT & Future Planning (NRF-2014R1A1A1006117 and No.2011-0030049), by a grant of the Korea Health Technology R&D Projectthrough the Korea Health Industry Development Institute (KHIDI), fundedby the Ministry of Health & Welfare, Republic of Korea (HI16C1653). Thefunders had role in study design, data collection and analysis, decisionto publish, or preparation of the manuscript in Life Science field.
abstract
Tuberculosis is a global health problem and at least one-third of the world's population is infected with Mycobacterium tuberculosis (MTB). MTB is a successful pathogen that enhances its own intracellular survival by inhibiting inflammation and arresting phago-lysosomal fusion. We previously demonstrated that Toxoplasma gondii (T. gondii) dense granule antigen (GRA) 7 interacts with TNF receptor-associated factor 6 via Myeloid differentiation primary response gene 88, enabling innate immune responses in macrophages. To extend these studies, we found that GRA7 interacts with host proteins involved in antimicrobial host defense mechanisms as a therapeutic strategy for tuberculosis. Here, we show that protein kinase C (PKC)alpha-mediated phosphorylation of T. gondii GRA7-I (Ser52) regulates the interaction of GRA7 with PYD domain of apoptosis-associated speck-like protein containing a carboxy- terminal CARD, which is capable of oligomerization and inflammasome activation can lead to antimicrobial defense against MTB. Furthermore, GRA7-III interacted with the PX domain of phospholipase D1, facilitating its enzyme activity, phago-lysosomal maturation, and subsequent antimicrobial activity in a GRA7-III (Ser135) phosphorylation-dependent manner via PKC alpha. Taken together, these results underscore a previously unrecognized role of GRA7 in modulating antimicrobial host defense mechanism during mycobacterial infection.
provenance
Made available in Cube on 2018-09-28T16:05:59Z (GMT). No. of bitstreams: 0
language
English
author
Koh, Hyun-Jung
Kim, Ye-Ram
Kim, Jae-Sung
Yun, Jin-Seung
Jang, Kiseok
Yang, Chul-Su
accessioned
2018-09-28T16:05:59Z
available
2018-09-28T16:05:59Z
issued
2017
citation
PLOS PATHOGENS(13): 1
issn
1553-7366
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486377.do
Funder
보건복지부
Funding Program
질환극복기술개발
Project ID
1465023617
Jurisdiction
Rep.of Korea
Project Name
Development of tuberculosis therapeutics based on intergrated networks of mycobacteria RD1-targeted host proteins
rights
openAccess
type
article


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