SOCS3-deficient lung epithelial cells uptaking neutrophil-derived SOCS3 worsens lung influenza infection

被引：4

作者：

Li, Ling ^{[1
]}

Wu, Haiya ^{[1
]}

Li, Qingmei ^{[1
]}

Chen, Jie ^{[1
]}

Xu, Kaifeng ^{[2
]}

Xu, Jinfu ^{[3
]}

Su, Xiao ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Pasteur Shanghai, Unit Resp Infect & Immun, B104,Life Sci Res Bldg,320 Yueyang Rd, Shanghai 200031, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Resp Med, Beijing 100730, Peoples R China

[3] Tongji Univ, Shanghai Pulm Hosp, Dept Pulm & Crit Care Med, Shanghai, Peoples R China

来源：

MOLECULAR IMMUNOLOGY | 2020年 / 125卷

关键词：

SOCS3; Influenza A virus; Lung infection; Lung epithelial cells; Neutrophils; GM-CSF; INJURY; VIRUS; MECHANISMS; EXPRESSION; PROTEINS; ACTIVATION; SUPPRESSOR; PARTICLES; PROTECTS;

D O I：

10.1016/j.molimm.2020.06.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of TBK1 and interferon pathway and the expression of SOCS3 is closely correlated with symptoms of influenza patients. However, whether deletion of Socs3 in the lung epithelial cells would affect influenza lung replication and inflammation in vivo is unknown. To test this, we approached the influenza infected Socs3(f/f) and SpcCre.Socs3(f/f) mice. We first found that knockdown of Socs3 in lung epithelial cells reduced influenza replication. However, in the in vivo study, there was a reduction of SOCS3 in the influenza-infected neutrophils coincided with an increase of SOCS3 in the CD45(-)CD326(+) lung epithelial cells in PR8-infected SpcCre.Socs3(f/f) mice. SOCS3-deficient neutrophils expressed higher levels of IL-17 that enhanced chemokine expression in the lung epithelial cells. Lung SOCS3-dificient epithelial cells increased expression of GM-CSF and PGE2 which promoted SpcCre.Socs3(f/f) neutrophils to yield SOCS3. SpcCre.Socs3(f/f) lung epithelial cells internalized SOCS3 released from GM-CSF + PGE(2)-stimulated SpcCre.Socs3(f/f) neutrophils, which could boost influenza replication in the lung epithelial cells. Thus, in the in vivo study, deletion of SOCS3 from lung epithelium could be nullified by the uptake from SOCS3 from infiltrated neutrophils. In addition, deletion of Socs3 from myeloid cells reduced lung influenza infection, but increased lung inflammation. Taken together, deletion of SOCS3 could suppress influenza replication, but intracellular SOCS3 communication between neutrophils and lung epithelial cells confounds this effect.

引用

页码：51 / 62

页数：12