Role of CXCL5 in Regulating Chemotaxis of Innate and Adaptive Leukocytes in Infected Lungs Upon Pulmonary Influenza Infection

Guo, Lei; Li, Nan; Yang, Zening; Li, Heng; Zheng, Huiwen; Yang, Jun; Chen, Yanli; Zhao, Xin; Mei, Junjie; Shi, Hongzhe; Worthen, G. Scott; Liu, Longding

doi:10.3389/fimmu.2021.785457

Cited by 23 publications

(13 citation statements)

References 40 publications

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“…37 ENA-78 is primarily a neutrophil chemoattractant, and counterintuitively, the expression of ENA-78 was higher in children infected with RV. 38 In the convalescence phase, the former differences observed in the acute phase were dissipated. However, in the convalescence phase (2 weeks later) the RV-HBoV1 group was demonstrated by decreased expression of fractalkine, MCP-3, and IL-8 when compared with the RV group.…”

Section: Discussionmentioning

confidence: 99%

“…TARC distinguishes itself by selectively binding to C‐C chemokine receptor type 4, thereby resulting in induction the of type 2 immune responses via, for example, ILC2, Th2 cells, and airway eosinophils 37 . ENA‐78 is primarily a neutrophil chemoattractant, and counterintuitively, the expression of ENA‐78 was higher in children infected with RV 38 …”

Section: Discussionmentioning

confidence: 99%

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Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus‐induced first wheezing episode in children

Hurme,

Sahla,

Rückert

et al. 2023

Clinical & Translational All

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BackgroundRhinovirus (RV)‐induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV‐induced immune responses in young children. We investigated cytokine profiles of sole RV‐ and dual RV‐HBoV1‐induced first wheezing episodes, and their association with severity and prognosis.MethodsFifty‐two children infected with only RV and nine children infected with dual RV‐HBoV1, aged 3–23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti‐CD3/anti‐CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years.ResultsThe mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL‐1b, MIP‐1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF‐a, TARC, and ENA‐78 in the RV‐HBoV1 group compared with the RV group. In the convalescence phase, the RV‐HBoV1 group was characterized by decreased expression of Fractalkine, MCP‐3, and IL‐8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p < 0.05), signifying that increased levels of epidermal growth factor and MIP‐1b were related with a shorter duration of hospitalization in the RV‐HBoV1 coinfection group but not in the RV group.ConclusionsDifferent cytokine response profiles were detected between the RV and the RV‐HBoV1 groups. Our results show the idea that RV‐induced immune responses may be suppressed by HBoV1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus‐induced first wheezing episode in children

Hurme,

Sahla,

Rückert

et al. 2023

Clinical & Translational All

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“…At study entry, children infected with RV were characterized by a higher expression of eotaxin-2 and TARC; the former promotes the migration of eosinophils into the lungs ( 27 ), and the latter selectively binds to CCR4, leading to the activation of a type 2 immune response via , e.g., Th2 cells, ILC2, and airway eosinophils ( 28 ). The expression of ENA-78, although counterintuitive is primarily a neutrophil chemoattractant, was higher in children infected with RV ( 29 ). Children infected with RSV were characterized by a higher activity of proinflammatory-associated cytokines IL-1β and its antagonist IL-1RA.…”

Section: Discussionmentioning

confidence: 99%

Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course

Hurme

Komulainen²,

Tulkki³

et al. 2022

Front. Immunol.

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Rhinovirus (RV) and respiratory syncytial virus (RSV) are common causes of bronchiolitis. Unlike an RSV etiology, an RV etiology is associated with a markedly increased risk of asthma. We investigated the cytokine profiles of RV- and RSV-induced first wheezing episode and their correlation with prognosis. We recruited 52 sole RV- and 11 sole RSV-affected children with a severe first wheezing episode. Peripheral blood mononuclear cells (PBMCs) were isolated during acute illness and 2 weeks later and stimulated in vitro with anti-CD3/anti-CD28. Culture medium samples were analyzed for 56 different cytokines by multiplex ELISA. Recurrences were prospectively followed for 4 years. In adjusted analyses, the cytokine response from PBMCs in the RV group was characterized by decreased expression of interleukin 1 receptor antagonist (IL-1RA), interleukin 1 beta (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) and increased expression of eosinophil chemotactic protein 2 (eotaxin-2), thymus- and activation-regulated chemokine (TARC), and epithelial-derived neutrophil-activating peptide 78 (ENA-78) in the acute phase and increased expression of fractalkine in the convalescent phase compared to those in the RSV group. An analysis of the change in cytokine expression between study points revealed an increased expression of fractalkine and IL-1β and decreased expression of I-309 (CCL1) and TARC in the RV group compared to those in the RSV group.. Considering hospitalization time, a significant non-adjusted group × cytokine interaction was observed in the levels of interferon gamma (IFN-γ), macrophage-derived chemokine (MDC), IL-1RA, and vascular endothelial growth factor (VEGF), indicating that a higher expression of cytokine was associated with shorter hospitalization time in the RSV group but not in the RV group. A significant interaction was also found in interleukin 6 (IL-6), but the cytokine response was not associated with hospitalization time in the RSV or RV group. In the RV group, increased expression of I-309 (CCL1) and TARC was associated with fewer relapses within 2 months, and decreased expression of interleukin 13 (IL-13) and increased expression of I-309 (CCL1) were associated with less relapses within 12 months. Differences in cytokine response from PBMCs were observed between RV- and RSV-induced first severe wheezing episode. Our findings also reveal new biomarkers for short- and medium-term prognosis in first-time wheezing children infected with RV or RSV.

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“…The CXCL1-3/CXCR2 biological axis is a critical facilitator of lung injury in this setting since neutrophil mobilization and pulmonary injury were reduced upon treatment of mice with anti-CXCR2 neutralizing antibody following prior exposure to dsRNA [ 144 ]. The CXCL5/CXCR2 axis might also be involved in the regulation of leukocyte mobilization after pulmonary influenza infection [ 145 ]. Reparixin, a CXCR2 inhibitor with a promising profile in the treatment of severe COVID-19 pneumonia, has completed a phase 3 clinical trial ( NCT04878055 ) in adult patients with the disease [ 146 ].…”

Section: The Role and Therapeutic Relevance Of CXC Motif Chemokines A...mentioning

confidence: 99%

“…e CXCL5/CXCR2 axis might also be involved in the regulation of leukocyte mobilization after pulmonary influenza infection [145]. Reparixin, a CXCR2 inhibitor with a promising profile in the treatment of severe COVID-19 pneumonia, has completed a phase 3 clinical trial (NCT04878055) in adult patients with the disease [146].…”

Section: Viral Pneumonia and Erapeutic Prospects Of Cxcrsmentioning

confidence: 99%

CXC Chemokines in the Pathogenesis of Pulmonary Disease and Pharmacological Relevance

Komolafe

Pacurari

2022

International Journal of Inflammation

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Chemokines and their receptors play important roles in the pathophysiology of many diseases by regulating the cellular migration of major inflammatory and immune players. The CXC motif chemokine subfamily is the second largest family, and it is further subdivided into ELR motif CXC (ELR+) and non-ELR motif (ELR-) CXC chemokines, which are effective chemoattractants for neutrophils and lymphocytes/monocytes, respectively. These chemokines and their receptors are expected to have a significant impact on a wide range of lung diseases, many of which have inflammatory or immunological underpinnings. As a result, manipulations of this subfamily of chemokines and their receptors using small molecular agents and other means have been explored for potential therapeutic benefit in the setting of several lung pathologies. Furthermore, encouraging preclinical data has necessitated the progression of a few of these drugs into clinical trials in order to make the most effective use of interventions in the development of viable targeted therapeutics. The current review presents the understanding of the roles of CXC ligands (CXCLs) and their cognate receptors (CXCRs) in the pathogenesis of several lung diseases such as allergic rhinitis, COPD, lung fibrosis, lung cancer, pneumonia, and tuberculosis. The potential therapeutic benefits of pharmacological or other CXCL/CXCR axis manipulations are also discussed.

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Role of CXCL5 in Regulating Chemotaxis of Innate and Adaptive Leukocytes in Infected Lungs Upon Pulmonary Influenza Infection

Cited by 23 publications

References 40 publications

Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus‐induced first wheezing episode in children

Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus‐induced first wheezing episode in children

Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course

CXC Chemokines in the Pathogenesis of Pulmonary Disease and Pharmacological Relevance

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