IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory Infection

IL-21/IL-21R was documented to participate in the regulation of multiple infection and inflammation. During Chlamydia muridarum (C. muridarum) respiratory infection, our previous study had revealed that the absence of this signal induced enhanced resistance to infection with higher protective Th1/Th...

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Main Authors: Jiajia Zeng, Yueyue Xu, Lu Tan, Xiaoyu Zha, Shuaini Yang, Hong Zhang, Yuqing Tuo, Ruoyuan Sun, Wenhao Niu, Gaoju Pang, Lida Sun, Hong Bai
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2022/4322092
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author Jiajia Zeng
Yueyue Xu
Lu Tan
Xiaoyu Zha
Shuaini Yang
Hong Zhang
Yuqing Tuo
Ruoyuan Sun
Wenhao Niu
Gaoju Pang
Lida Sun
Hong Bai
author_facet Jiajia Zeng
Yueyue Xu
Lu Tan
Xiaoyu Zha
Shuaini Yang
Hong Zhang
Yuqing Tuo
Ruoyuan Sun
Wenhao Niu
Gaoju Pang
Lida Sun
Hong Bai
author_sort Jiajia Zeng
collection DOAJ
description IL-21/IL-21R was documented to participate in the regulation of multiple infection and inflammation. During Chlamydia muridarum (C. muridarum) respiratory infection, our previous study had revealed that the absence of this signal induced enhanced resistance to infection with higher protective Th1/Th17 immune responses. Here, we use the murine model of C. muridarum respiratory infection and IL-21R deficient mice to further identify a novel role of IL-21/IL-21R in neutrophilic inflammation. Resistant IL-21R-/- mice showed impaired neutrophil recruitment to the site of infection. In the absence of IL-21/IL-21R, pulmonary neutrophils also exhibited reduced activation status, including lower CD64 expression, MPO activity, and neutrophil-produced protein production. These results correlated well with the decrease of neutrophil-related chemokines (KC and MIP-2), inflammatory cytokines (IL-6, IL-1β, and TNF-α), and TLR/MyD88 pathway mediators (TLR2, TLR4, and MyD88) in infected lungs of IL-21R-/- mice than normal mice. Complementarily, decreased pulmonary neutrophil infiltration, activity, and levels of neutrophilic chemotactic factors and TLR/MyD88 signal in infected lungs can be corrected by rIL-21 administration. These results revealed that IL-21/IL-21R may aggravate the neutrophil inflammation through regulating TLR/MyD88 signal pathway during chlamydial respiratory infection.
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spelling doaj-art-8ce2f3173d544a9288ae67e8ecfcfd302025-08-20T03:37:44ZengWileyMediators of Inflammation1466-18612022-01-01202210.1155/2022/4322092IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory InfectionJiajia Zeng0Yueyue Xu1Lu Tan2Xiaoyu Zha3Shuaini Yang4Hong Zhang5Yuqing Tuo6Ruoyuan Sun7Wenhao Niu8Gaoju Pang9Lida Sun10Hong Bai11Department of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyIL-21/IL-21R was documented to participate in the regulation of multiple infection and inflammation. During Chlamydia muridarum (C. muridarum) respiratory infection, our previous study had revealed that the absence of this signal induced enhanced resistance to infection with higher protective Th1/Th17 immune responses. Here, we use the murine model of C. muridarum respiratory infection and IL-21R deficient mice to further identify a novel role of IL-21/IL-21R in neutrophilic inflammation. Resistant IL-21R-/- mice showed impaired neutrophil recruitment to the site of infection. In the absence of IL-21/IL-21R, pulmonary neutrophils also exhibited reduced activation status, including lower CD64 expression, MPO activity, and neutrophil-produced protein production. These results correlated well with the decrease of neutrophil-related chemokines (KC and MIP-2), inflammatory cytokines (IL-6, IL-1β, and TNF-α), and TLR/MyD88 pathway mediators (TLR2, TLR4, and MyD88) in infected lungs of IL-21R-/- mice than normal mice. Complementarily, decreased pulmonary neutrophil infiltration, activity, and levels of neutrophilic chemotactic factors and TLR/MyD88 signal in infected lungs can be corrected by rIL-21 administration. These results revealed that IL-21/IL-21R may aggravate the neutrophil inflammation through regulating TLR/MyD88 signal pathway during chlamydial respiratory infection.http://dx.doi.org/10.1155/2022/4322092
spellingShingle Jiajia Zeng
Yueyue Xu
Lu Tan
Xiaoyu Zha
Shuaini Yang
Hong Zhang
Yuqing Tuo
Ruoyuan Sun
Wenhao Niu
Gaoju Pang
Lida Sun
Hong Bai
IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory Infection
Mediators of Inflammation
title IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory Infection
title_full IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory Infection
title_fullStr IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory Infection
title_full_unstemmed IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory Infection
title_short IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory Infection
title_sort il 21 il 21r regulates the neutrophil mediated pathologic immune response during chlamydial respiratory infection
url http://dx.doi.org/10.1155/2022/4322092
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