Alveolar-like Macrophages Attenuate Respiratory Syncytial Virus Infection

Porto, Bárbara Nery; Litvack, Michael; Cen, Yuchen; Lok, Irene; Bouch, Sheena; Norris, Michael; Duan, Wenming; Ackerley, Cameron; Post, Martin; Moraes, Theo J.

doi:10.3390/v13101960

Cited by 4 publications

(6 citation statements)

References 49 publications

(65 reference statements)

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“…Importantly, macrophage polarization is also likely involved in RSV infection ( 66 , 67 ). Although there is evidence showing that alveolar macrophages necroptosis drives disease pathogenesis during RSV infection ( 68 ), there are also evidence indicating that AM can control/attenuate RSV pathology ( 44 , 68 – 71 ). Our study showed that OM–85 treatment used as preventive measure consistently maintained AM population in the lungs, while RSV–infected untreated animals presented a pronounced reduction in these cells.…”

Section: Discussionmentioning

confidence: 99%

Airway Administration of Bacterial Lysate OM-85 Protects Mice Against Respiratory Syncytial Virus Infection

et al. 2022

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Respiratory syncytial virus (RSV) is a seasonal pathogen responsible for the highest percentage of viral bronchiolitis in pediatric patients. There are currently no vaccine available and therapeutic methods to mitigate the severity of RSV bronchiolitis are limited. OM-85, an oral standardized bacterial lysate isolated from human respiratory strains and widely used to prevent recurrent infections and/or exacerbations in populations at risk, has been shown to be effective and safe in children and adults. Here, we demonstrate that airway administration of OM-85 in Balb/c mice prior to infection prevents RSV-induced disease, resulting in inhibition of viral replication associated with less perivascular and peribronchial inflammation in the lungs. These protective effects are dose and time-dependent with complete protection using 1mg dose of OM-85 only four times intranasally. Mechanistic insights using this topical route in the airways revealed increased alveolar macrophages, a selective set of tolerogenic DCs, Treg and Th1 expansion in the lung, even in the absence of infection, contributing to a better Th1/Th2 balance and preventing ILC2 recruitment in the airways and associated inflammatory sequelae. OM-85 preventive treatment also improved antiviral response by increasing IFNβ and its responsive genes in the lung. In vitro, OM-85 protects against RSV infection in a type I interferon pathway. Our animal model data suggest that intranasal use of OM-85 should be considered as a potential prophylactic product to prevent RSV bronchiolitis once human studies confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Airway Administration of Bacterial Lysate OM-85 Protects Mice Against Respiratory Syncytial Virus Infection

et al. 2022

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“… 17 and kill respiratory syncytial virus (RSV) and prevent RSV‐induced lung injury. 18 Here, we further characterized ALMs for their efficacy to treat bacterial lung infections. We evaluated the non‐pharmacological antimicrobial functions of ALMs, specifically for bacteria known to colonize the lungs of immune‐compromised individuals, such as P .…”

Section: Introductionmentioning

confidence: 99%

“…A . ) 17 and kill respiratory syncytial virus (RSV) and prevent RSV‐induced lung injury 18 . Here, we further characterized ALMs for their efficacy to treat bacterial lung infections.…”

Section: Introductionmentioning

confidence: 99%

“…17 Previously, we have demonstrated that ALMs reduce lung injury in mouse models of acute and chronic lung diseases, can internalize dead Staphylococcus aureus (S.A.) 17 and kill respiratory syncytial virus (RSV) and prevent RSV-induced lung injury. 18 Here, we further characterized ALMs for their efficacy to treat bacterial lung infections. We evaluated the non-pharmacological antimicrobial functions of ALMs, specifically for bacteria known to colonize the lungs of immune-compromised individuals, such as P.A.…”

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confidence: 99%

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Therapeutic stem cell‐derived alveolar‐like macrophages display bactericidal effects and resolve Pseudomonas aeruginosa‐induced lung injury

Bouch

Litvack

Litman

et al. 2022

J Cellular Molecular Medi

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Communicable bacterial lung infections affect hundreds of millions of individuals, with respiratory infections being the leading cause of death in developing countries accounting for greater than 4 million deaths per year. 1 Common bacterial infections and diseases include pneumonia, tuberculosis and pertussis; however, patients with compromised lung immunity, such as individuals with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD) and lung transplant recipients, are particularly

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“…To determine the role of macrophages in RSV infection, in vivo models have typically been used that deplete alveolar macrophages, or adoptively transfer specific types of macrophages into the lungs again after depletion. However, there are conflicting findings in these reports, with some suggesting macrophages are protective [ 23 – 26 ], while others suggest they contribute to the pathology [ 27 , 28 ] of infection. To add to the complexity, modifying the phenotype of alveolar macrophage during infection may also provide a protective effect against viral infection [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

M1-like, but not M0- or M2-like, macrophages, reduce RSV infection of primary bronchial epithelial cells in a media-dependent fashion

Ronaghan

Soo²,

Pena³

et al. 2022

PLoS ONE

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Respiratory syncytial virus (RSV) is a common childhood infection that in young infants can progress into severe bronchiolitis and pneumonia. Disease pathogenesis results from both viral mediated and host immune processes of which alveolar macrophages play an important part. Here, we investigated the role of different types of alveolar macrophages on RSV infection using an in vitro co-culture model involving primary tissue-derived human bronchial epithelial cells (HBECs) and human blood monocyte-derived M0-like, M1-like, or M2-like macrophages. It was hypothesized that the in vitro model would recapitulate previous in vivo findings of a protective effect of macrophages against RSV infection. It was found that macrophages maintained their phenotype for the 72-hour co-culture time period and the bronchial epithelial cells were unaffected by the macrophage media. HBEC infection with RSV was decreased by M1-like macrophages but enhanced by M0- or M2-like macrophages. The medium used during the co-culture also impacted the outcome of the infection. This work demonstrates that alveolar macrophage phenotypes may have differential roles during epithelial RSV infection, and demonstrates that an in vitro co-culture model could be used to further investigate the roles of macrophages during bronchial viral infection.

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Alveolar-like Macrophages Attenuate Respiratory Syncytial Virus Infection

Cited by 4 publications

References 49 publications

Airway Administration of Bacterial Lysate OM-85 Protects Mice Against Respiratory Syncytial Virus Infection

Airway Administration of Bacterial Lysate OM-85 Protects Mice Against Respiratory Syncytial Virus Infection

Therapeutic stem cell‐derived alveolar‐like macrophages display bactericidal effects and resolve Pseudomonas aeruginosa‐induced lung injury

M1-like, but not M0- or M2-like, macrophages, reduce RSV infection of primary bronchial epithelial cells in a media-dependent fashion

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