Rapid GPR183-mediated recruitment of eosinophils to the lung after Mycobacterium tuberculosis infection

Carpenter, Andrea C.; Castro, Ehydel; Tocheny, Claire E.; Assmann, Maike; Schwarz, Benjamin; Bohrnsen, Eric; Makiya, Michelle; Legrand, Fanny; Hilligan, Kerry L.; Baker, Paul J.; Torres-Juárez, Flor; Hu, Zhidong; Ma, Hui; Wang, Lin; Niu, Liangfei; Zhu, Wen; Lee, Sang H.; Kamenyeva, Olena; Kauffman, Keith D.; Donato, Michèle; Sher, Alan; Barber, Daniel L.; Via, Laura E.; Scriba, Thomas J.; Khatri, Purvesh; Song, Yanzheng; Wong, Ka-Wing; Bosio, Catharine M.; Klion, Amy D.; Mayer‐Barber, Katrin D.

doi:10.1016/j.celrep.2022.111144

Cited by 25 publications

(22 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently showed in a murine model of Mycobacterium tuberculosis (Mtb) infection that both GPR183 and the 725-OHC-producing enzyme CYP7B1 are required for rapid macrophage infiltration into the lung upon mycobacterial infection [18]. In the Mtb model, GPR183 was also required for infiltration of eosinophils [14]. We identified both alveolar macrophages and infiltrating macrophages as the predominant cell type expressing CH25H and CYP7B1 upon Mtb infection [18] and corroborated this here with the scRNASeq data from COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

“…7α,25-OHC is the endogenous high affinity agonist of the oxysterol-sensing G protein-coupled receptor GPR183 [11,12]. GPR183 is expressed on cells of the innate and adaptive immune systems, including macrophages, dendritic cells, innate lymphoid cells, eosinophils and T and B lymphocytes [5,13,14]. With its oxysterol ligands GPR183 facilitates the chemotactic distribution of immune cells to secondary lymphoid organs [9,11,13,15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection

et al. 2022

View full text Add to dashboard Cite

RationaleSevere viral respiratory infections are often characterised by extensive myeloid cell infiltration and activation and persistent lung tissue injury. However, the immunological mechanisms driving excessive inflammation in the lung remain poorly understood.ObjectivesTo identify the mechanisms that drive immune cell recruitment in the lung during viral respiratory infections and identify novel drug targets to reduce inflammation and disease severity.MethodsPreclinical murine models of influenza virus and severe acute respiratory coronavirus 2 (SARS-CoV-2) infection.ResultsOxidised cholesterols and the oxysterol-sensing receptor GPR183 were identified as drivers of monocyte-macrophage infiltration to the lung during influenza virus (IAV) and SARS-CoV-2 infection. Both IAV and SARS-CoV-2 infection upregulated the enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) in the lung, resulting in local production of the oxidised cholesterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC). Loss-of-function mutation of GPR183, or treatment with a GPR183 antagonist, reduced macrophage infiltration and inflammatory cytokine production in the lungs of IAV- or SARS-CoV-2-infected mice. The GPR183 antagonist significantly attenuated the severity of SARS-CoV-2 infection and viral loads. Analysis of single cell RNASeq data on bronchoalveolar lavage samples from healthy controls and COVID-19 patients with moderate and severe disease revealed thatCH25H, CYP7B1andGPR183are significantly upregulated in macrophages during COVID-19.ConclusionThis study demonstrates that oxysterols drive inflammation in the lungviaGPR183 and provides the first preclinical evidence for therapeutic benefit of targeting GPR183 during severe viral respiratory infections.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection

et al. 2022

View full text Add to dashboard Cite

show abstract

“…It has been hypothesized that SARS-CoV-2 infection activates eosinophils, which then migrate to the lungs and in turn are lysed [ 33 ]. This lysis causes phagocyte recruitment, and this process may trigger hyperinflammation and a cytokine storm [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Mepolizumab as a Potential Protective Factor of COVID-19 Mortality: A Case Report of Chronic Bronchitis and Asthma in an Elderly Patient

et al. 2022

View full text Add to dashboard Cite

Unusual clinical course Background:Patients with multiple comorbidities who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have a higher risk of mortality. However, treatment with mepolizumab may be a key factor in counteracting the risk of these comorbidities. We present a patient who had an uneventful recovery from coronavirus disease 2019 (COVID-19), despite having 5 independent risk factors for severe disease and increased mortality. Case Report:A 75-year-old man with a long-standing history of asthma, chronic bronchitis, coronary artery disease, and hypertension presented to the Emergency Department in November 2020 with a 4-day history of fever, chills, shortness of breath, cough, and fatigue. Six months prior to this presentation, the patient was hospitalized for severe chronic bronchitis and acute exacerbation of asthma. His medications included mepolizumab, aclidinium, ramipril, diltiazem, aspirin, albuterol sulfate, and micronized budesonide/micronized formoterol fumarate dihydrate. Physical examination was unremarkable, except for cardiopulmonary distress. Laboratory tests showed leucocytosis. His chest X-ray revealed infiltrates and interstitial edema in the lower lung fields. A PCR test for SARS-CoV-2 was positive. COVID-19 pneumonia was diagnosed, and the patient was admitted to the hospital, where he was treated with acetaminophen, amoxicillin, dexamethasone, and supplemental oxygen. The patient remained stable and was discharged from the hospital the following day. He was free of all symptoms after 21 days. Conclusions:This case of a 75-year-old man who presented with mild COVID-19 supports the findings from other reports of improvement in clinical outcomes for some patients with asthma who received treatment with mepolizumab.

show abstract

“…The recruitment of innate lymphoid cells to cryptopatches and isolated lymphoid follicles in the mice colon during inflammation is also driven by GPR183 and 7α, 25‐OHC [82, 83]. Indeed, two recent studies in mice have demonstrated the important role of GPR183 in Mtb infection [84, 85]. The first study has reported that GPR183 mediates the migration and accumulation of eosinophils into pulmonary lesions resulting from a type II inflammatory response in Mtb infection to support the host immune response [85].…”

Section: The Modulatory Mechanisms Of Cholesterol‐autoxidation Metabo...mentioning

confidence: 99%

Cholesterol‐autoxidation metabolites in host defense against infectious diseases

Shi

Zhan

et al. 2023

Eur J Immunol

View full text Add to dashboard Cite

Cholesterol plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized to oxysterols by enzymatic or nonenzymatic ways. Nonenzymatic cholesterol metabolites, also called cholesterol‐autoxidation metabolites, are formed dependent on the oxidation of reactive oxygen species (ROS) such as OH• or reactive nitrogen species, such as ONOO−. Cholesterol‐autoxidation metabolites are abundantly produced in diseases such as inflammatory bowel disease and atherosclerosis, which are associated with oxidative stress. Recent studies have shown that cholesterol‐autoxidation metabolites can further regulate the immune system. Here, we review the literature and summarize how cholesterol‐autoxidation metabolites, such as 25‐hydroxycholesterol (25‐OHC), 7α/β‐OHC, and 7‐ketocholesterol, deal with the occurrence and development of infectious diseases through pattern recognition receptors, inflammasomes, ROS production, nuclear receptors, G‐protein‐coupled receptor 183, and lipid availability. In addition, we include the research regarding the roles of these metabolites in COVID‐19 infection and discuss our viewpoints on the future research directions.

show abstract

Rapid GPR183-mediated recruitment of eosinophils to the lung after Mycobacterium tuberculosis infection

Cited by 25 publications

References 67 publications

GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection

GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection

Mepolizumab as a Potential Protective Factor of COVID-19 Mortality: A Case Report of Chronic Bronchitis and Asthma in an Elderly Patient

Cholesterol‐autoxidation metabolites in host defense against infectious diseases

Contact Info

Product

Resources

About