CCR5 attenuates neutrophilic airway inflammation exacerbated by infection with rhinovirus

Hossain, Ferdaus Mohd Altaf; Park, Seong Ok; Kim, Hyo Jin; Eo, Jun Cheol; Choi, Jin Young; Uyangaa, Erdenebelig; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

doi:10.1016/j.cellimm.2020.104066

Cited by 9 publications

(22 citation statements)

References 58 publications

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“…Juan-juan et al observed a trend of increased IL-1β gene and protein expression in asthmatics with frequent exacerbations [ 12 ]. IL-1β was also confirmed to be involved in the viral stimulus-induced asthma exacerbation [ 21 , 22 ]. Due to the small sample size of asthmatics with at least one exacerbation during six months of follow-up period (only three patients), we could not analyze the relationship between IL-1β mRNA expression and asthma exacerbation in our study.…”

Section: Discussionmentioning

confidence: 99%

IL-1β augments TGF-β inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics

Zhang

Fan²,

Qin

et al. 2021

Respir Res

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Background Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA. Methods Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1β, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1β in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1β mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells. Results NA had increased baseline sputum cell IL-1β expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV1 compared to EA. For all asthmatics, sputum IL-1β mRNA was positively correlated with protein expression. Sputum IL-1β mRNA and protein levels were negatively correlated to FEV1 improvement. After subgrouping, the correlation between IL-1β mRNA and FEV1 improvement was significant in NA but not in EA. Thickness of RBM in asthmatics was greater than that of healthy controls and positively correlated with neutrophil percentage in bronchoalveolar lavage fluid. In vitro experiments, the process of IL-1β augmenting TGF-β1-induced EMT cannot be abrogated by glucocorticoid or montelukast sodium, but can be reversed by MAPK inhibitors. Conclusions IL-1β level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1β augmenting TGF-β1-induced steroid-resistant EMT through MAPK signaling pathways. Trial registration: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406).

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Section: Discussionmentioning

confidence: 99%

IL-1β augments TGF-β inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics

Zhang

Fan²,

Qin

et al. 2021

Respir Res

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“…Zachova et al (2019) showed that Epstein-Barr virus (EBV)-infected B cells have increased CCR5 expression compared to EBV-non-infected cells. Also, recent evidence points to a pivotal role of the CCR5 in the attenuation of rhinovirus-associated inflammation, by controlling the activity of CD4 + Foxp3 + Treg cells (Hossain et al, 2020). Altered levels of cytokines and chemokines are associated with several aspects of ZIKV (Barros et al, 2018;Naveca et al, 2018;Khaiboullina et al, 2019;Lima et al, 2019), EBV (Piovan et al, 2005;Ehlin-Henriksson et al, 2009;Cohen et al, 2017), and rhinovirus infections (Rajan et al, 2014;Shelfoon et al, 2016;Hansel et al, 2017).…”

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confidence: 99%

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

et al. 2020

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The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human CC chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. Subsequently, this review addresses the impacts of CCR5 gene editing and CCR5 modulation on health and viral diseases. Also, this article connects recent findings regarding extracellular vesicles (e.g., exosomes), viruses, and CCR5. Neglected and emerging topics in "CCR5 research" are briefly described, with focus on Rocio virus, Zika virus, Epstein-Barr virus, and Rhinovirus. Finally, the potential influence of CCR5 on the immune responses to coronaviruses is discussed.

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“…Mouse models of asthma exacerbations caused by hRV infection were established as described elsewhere, with some modification ( 39 ). The experimental WT BL/6 and IDO KO mice were sensitized with 100 μg of chicken OVA (Grade V; Sigma-Aldrich) absorbed to 2 mg of aluminum hydroxide (alum; Sigma-Aldrich) in a volume of 200 μl of PBS via intraperitoneal (i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…BALF was collected 1 or 2 days after the last OVA challenge and hRV infection, as described elsewhere ( 39 ). Briefly, mice were anesthetized by an intramuscular injection of Zolazepam (Zoletil 50; Virbac, Carros, France) before a thoracotomy.…”

Section: Methodsmentioning

confidence: 99%

“…Airway responsiveness was measured 24 h after the hRV-induced asthma exacerbation by recording respiratory pressure curves using barometric unrestrained whole-body plethysmography (Buxco; EMKA Technologies, Paris, France) following inhalation of methacholine (acetyl-β-methyl-choline chloride, Sigma-Aldrich) by conscious, unrestrained mice. Airway responsiveness was expressed as enhanced pause (Penh value), as described elsewhere ( 39 ). Briefly, mice were placed in a whole-body chamber, and basal readings were obtained and averaged for a 5-min period.…”

Section: Methodsmentioning

confidence: 99%

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Indoleamine 2,3-Dioxygenase in Hematopoietic Stem Cell-Derived Cells Suppresses Rhinovirus-Induced Neutrophilic Airway Inflammation by Regulating Th1- and Th17-Type Responses

et al. 2021

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Asthma exacerbations are a major cause of intractable morbidity, increases in health care costs, and a greater progressive loss of lung function. Asthma exacerbations are most commonly triggered by respiratory viral infections, particularly with human rhinovirus (hRV). Respiratory viral infections are believed to affect the expression of indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in tryptophan catabolism, which is presumed to alter asthmatic airway inflammation. Here, we explored the detailed role of IDO in the progression of asthma exacerbations using a mouse model for asthma exacerbation caused by hRV infection. Our results reveal that IDO is required to prevent neutrophilic inflammation in the course of asthma exacerbation caused by an hRV infection, as corroborated by markedly enhanced Th17- and Th1-type neutrophilia in the airways of IDO-deficient mice. This neutrophilia was closely associated with disrupted expression of tight junctions and enhanced expression of inflammasome-related molecules and mucin-inducing genes. In addition, IDO ablation enhanced allergen-specific Th17- and Th1-biased CD4 + T-cell responses following hRV infection. The role of IDO in attenuating Th17- and Th1-type neutrophilic airway inflammation became more apparent in chronic asthma exacerbations after repeated allergen exposures and hRV infections. Furthermore, IDO enzymatic induction in leukocytes derived from the hematopoietic stem cell (HSC) lineage appeared to play a dominant role in attenuating Th17- and Th1-type neutrophilic inflammation in the airway following hRV infection. Therefore, IDO activity in HSC-derived leukocytes is required to regulate Th17- and Th1-type neutrophilic inflammation in the airway during asthma exacerbations caused by hRV infections.

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CCR5 attenuates neutrophilic airway inflammation exacerbated by infection with rhinovirus

Cited by 9 publications

References 58 publications

IL-1β augments TGF-β inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics

IL-1β augments TGF-β inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

Indoleamine 2,3-Dioxygenase in Hematopoietic Stem Cell-Derived Cells Suppresses Rhinovirus-Induced Neutrophilic Airway Inflammation by Regulating Th1- and Th17-Type Responses

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