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Title 

Fas-associated factor 1 mediates NADPH oxidase-induced reactive oxygen species production and proinflammatory responses in macrophages against listeria infection

Authors 

T H KimH C LeeJae Hoon KimC Y HewawadugeK ChathurangaW A G ChathurangaP EkanayakaH M S M WijerathneC J KimE KimJ S Lee

Publisher 

Public Library of Science

Issue Date 

2019

Citation 

Plos Pathogens

Abstract 

Fas-associated factor 1 is a death-promoting protein that induces apoptosis by interacting with the Fas receptor. Until now, FAF1 was reported to interact potentially with diverse proteins and to function as a negative and/or positive regulator of several cellular possesses. However, the role of FAF1 in defense against bacterial infection remains unclear. Here, we show that FAF1 plays a pivotal role in activating NADPH oxidase in macrophages during Listeria monocytogenes infection. Upon infection by L. monocytogenes, FAF1 interacts with p67phox (an activator of the NADPH oxidase complex), thereby facilitating its stabilization and increasing the activity of NADPH oxidase. Consequently, knockdown or ectopic expression of FAF1 had a marked effect on production of ROS, proinflammatory cytokines, and antibacterial activity, in macrophages upon stimulation of TLR2 or after infection with L. monocytogenes. Consistent with this, FAF1gt/gt mice, which are knocked down in FAF1, showed weaker inflammatory responses than wild-type mice; these weaker responses led to increased replication of L. monocytogenes. Collectively, these findings suggest that FAF1 positively regulates NADPH oxidase-mediated ROS production and antibacterial defenses.

URI 

https://doi.org/10.1371/journal.ppat.1008004

ISSN 

1553-7366

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-10-29


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