IL-27/IL-27R Mediates Protective Immunity against Chlamydial Infection by Suppressing Excessive Th17 Responses and Reducing Neutrophil Inflammation

Zha, Xiaoyu; Yang, Shicheng; Niu, Wenhao; Tan, Lu; Xu, Yingxin; Zeng, Jiajia; Tang, Yingying; Sun, Lida; Pang, Gaoju; Qiao, Sai; Zhang, Hong; Liu, Tengli; Zhao, Huanyu; Zheng, Ningbo; Zhang, Yongci; Bai, Hong

doi:10.4049/jimmunol.2000957

Cited by 12 publications

(24 citation statements)

References 43 publications

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“…To determine the participation of FcγRI in chlamydial infection, we employed our established model of chlamydial respiratory infection by intranasal injection of C. muridarum into C57 BL/6 mice as previously described [ 10 , 16 ]. As the 3 days post-infection (3 d p.i.…”

Section: Resultsmentioning

confidence: 99%

“…For histopathological analyses, C. muridarum -infected lung tissues were fixed in 4% paraformaldehyde (PFA) (Life-iLab, Shanghai, China) and routinely embedded in paraffin, sectioned (5 μm), and stained with hematoxylin and eosin (H&E) according to the manufacturer’s instructions (Solarbio). The pathological changes were evaluated by the semi-quantitative histology score in a blinded manner as described previously [ 16 ]. Briefly, the inflammatory grades were scored as: score 0, normal; score 1, moderate and limited inflammatory granuloma with less than 25% cell infiltration and no obvious infiltration in adjacent alveolar septa or air space; score 2, moderate interstitial pneumonia with 25–50% cell infiltration and septal congestion and septal edema; score 3, inflammatory cells infiltrated into perivascular, peribronchiolar, alveolar septa and air space, accounting for 50–75% of the area; score 4, over 75% of the lung area infiltrated with inflammatory cells.…”

Section: Methodsmentioning

confidence: 99%

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A Pathogenic Role for FcγRI in the Immune Response against Chlamydial Respiratory Infection

et al. 2022

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FcγRI is an important cell surface receptor reported to be involved in multiple immune responses, although it has not yet been extensively studied in intracellular bacterial infections. Here, using a mouse model of C. muridarum respiratory infection, we were able to determine how FcγRI regulates the host resistance against chlamydial invasion. According to our findings, the chlamydial loads and pulmonary pathology were both reduced in FcγRI deficient (Fcgr1−/−) animals. Being infected, monocytes, macrophages, neutrophils, DCs, CD4+/CD8+ T cells, and effector Th1 subsets displayed increased FcγRI expression patterns. Altered infiltration of these cells in the lungs of Fcgr1−/− mice further demonstrated the regulation of FcγRI in the immune system and identified Th1 cells and macrophages as its target cell populations. As expected, we observed that the Th1 response was augmented in Fcgr1−/− mice, while the pro-inflammatory M1 macrophage polarization was constrained. These findings might indicate FcγRI as a potential regulator for host immunity and inflammatory response during chlamydial infection.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Pathogenic Role for FcγRI in the Immune Response against Chlamydial Respiratory Infection

et al. 2022

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“…Indeed, the double-bladed sword impact of IL-17 on host defense against C. muridarum respiratory infection was reported by our previous studies, Bai et al firstly demonstrated that moderate IL-17/Th17 response promoted protective type 1 T cell immunity by modulating DC function [ 43 ]. However, Zha et al founded that excessive IL-17/Th17 response caused increased neutrophil inflammation and contributed to severer disease when IL-27R deficient [ 26 ]. In this model, the inconsistency between higher IL-17 production and reduced neutrophil recruitment could be explained by the diversity of neutrophil chemotactic factors.…”

Section: Discussionmentioning

confidence: 99%

“…However, persistent robust effector functions may also lead to neutrophil-mediated tissue damages at infected sites [ 21 ], suggesting the dual role of neutrophils in inflammation. In chlamydial infection, the role of neutrophils in chlamydia-induced pathology has been revealed [ 22 – 26 ]. Using the plasmid-deficient strain of C. muridarum , Frazer et al found that enhanced neutrophil longevity and recruitment contributed to the severity of oviduct pathology [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…Our previous data have shown that C. muridarum infection induced pulmonary damage with significant neutrophil infiltration in susceptible C3H mice [ 25 ]. Further, in another study on the role of IL-27/IL-27R in chlamydial respiratory infection, we found that IL-27R knockout mice (WSX-1 −/− mice) suffered more severe disease with excessive IL-17-producing CD4 + T cells, and there are many more neutrophils and neutrophil-related chemotactic factors in lungs [ 26 ], which further suggested the pathologic tissue damage induced by massive neutrophil infiltration in chlamydial respiratory infection.…”

Section: Introductionmentioning

confidence: 99%

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

Zeng

Tan

et al. 2022

Mediators of Inflammation

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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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IL-27 Alleviates Airway Inflammation and Airway Hyperresponsiveness in Asthmatic Mice by Targeting the CD39/ATP Axis of Dendritic Cells

Chen,

Zhu,

et al. 2023

Inflammation

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Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been fully elucidated. This study aimed to examine whether IL-27 regulated the CD39/ATP axis of dendritic cells in asthma. Our results showed that in ovalbumin (OVA)-induced asthma mouse model, IL-27Rα−/− asthmatic mice showed increased airway resistance, increased infiltration of inflammatory cells in lung tissue, proliferation of goblet cells, enhanced expression of Muc5 AC around airway epithelium, increased total number of cells and eosinophils, increased levels of total IgE, OVA-IgE, IL-4, IL-5, IL-13 and IL-17 A, and increased expression of transcription factors GATA-3 and RORγt in lung tissue. The expression of CD39 mRNA and protein in the lung tissue of IL-27Rα−/− asthmatic mice decreased, and the expression of NLRP3, ASC and Caspase-1 in NLRP3 inflammasome components increased. The concentration of ATP was significantly increased compared with WT asthmatic mice. In vitro experiments showed that the expression of CD39 in lung dendritic cells of IL-27Rα−/− asthmatic mice decreased, while the expression of NLRP3 inflammasome components NLRP3, ASC and Caspase-1 increased. These findings indicate that IL-27 directly and indirectly regulates immunoinflammatory responses in asthma by acting on dendritic cells CD39/ATP Axis.

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IL-27/IL-27R Mediates Protective Immunity against Chlamydial Infection by Suppressing Excessive Th17 Responses and Reducing Neutrophil Inflammation

Cited by 12 publications

References 43 publications

A Pathogenic Role for FcγRI in the Immune Response against Chlamydial Respiratory Infection

A Pathogenic Role for FcγRI in the Immune Response against Chlamydial Respiratory Infection

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

IL-27 Alleviates Airway Inflammation and Airway Hyperresponsiveness in Asthmatic Mice by Targeting the CD39/ATP Axis of Dendritic Cells

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