Protective role of surface Toll-like receptor 9 expressing neutrophils in local inflammation during systemic inflammatory response syndrome in mice

S01615890.gif

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Xiuping Meng, Wei Sun, Yunjia Ren, Yue Xiao, Peiyan Zhao, Wenting Lu, Li Hua, Luowei Wang, Liying Wang, Yongli Yu
Clinically, systemic inflammatory response syndrome (SIRS) occurs after serious trauma or sepsis. In sepsis, neutrophils are the major effector cells responsible for eliminating pathogens. However, the role of neutrophils in development of SIRS, especially in local inflammatory area, is controversial. In this study, we established a SIRS mouse model characterized with cytokine-mediated lethal shock by intraperitoneal injection of oligodexynucleotides containing CpG motifs (CpG ODN) in D-galactosamine (D-GalN) sensitized mice based on our previous work and found that abundant neutrophils were rapidly recruited into the peritoneal cavity, where some neutrophils expressed surface TLR9 (sTLR9), defined as sTLR9+ neutrophils. Along with the progression of SIRS, the expression of sTLR9 in sTLR9+ neutrophils isolated from peritoneal lavage cells (PLCs) was declined in accompany with an increase in the level of the inflammatory cytokine TNFα and a decrease in the level of the anti-inflammatory cytokine IL-10 in Ly6G+ PLCs. When using CCT ODN, an oligodeoxynucleotide with CCT repeats, which we have previously shown to be capable of rescuing mice from lethal shock, the expression of sTLR9 on neutrophils was significantly elevated. Adoptive therapy using early recruited neutrophil-rich PLCs containing sTLR9+ neutrophils that express high levels of sTLR9, could rescue mice from SIRS. Overall, the data reveal that the early recruited sTLR9+ neutrophils may, at least in the area of local inflammation, play a protective role during SIRS development and provide a method to rescue the patients with severe SIRS via the up-regulation of sTLR9 levels on the surface of neutrophils or via adoptive therapy with protective sub-populations of neutrophils.

http://ift.tt/2tDfXSE

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s