Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis

Antunes, Krist Helen; Stein, Renato T.; Franceschina, Caroline Marinho; Silva, Emanuelle F. da; Freitas, Deise Nascimento de; Silveira, Josiane Silva; Mocellin, Magáli; Leitão, Lidiane Alves de Azeredo; Fachi, José Luís; Pral, Laís Passarielo; González, A. Muñoz; Oliveira, Sandro de; Duarte, Leonardo Teixeira Domingues; Cassão, Gisele; Gonçalves, João Ismael Budelon; Reis, Tatiane M; Abbadi, Bruno Lopes; Dornelles, Maiele; Sperotto, Nathalia Denise de Moura; Rigo, Maurício; Rodrigues, Hosana Gomes; Jones, Marcus B.; Epifânio, Matias; Guima, Suzana Eiko Sato; Setúbal, João Carlos; Jorge, Taíssa R.; Mansur, Daniel S; Mayer, Fabiana Quoos; Varela, Ana Paula Muterle; Bizarro, Cristiano Valim; Machado, Pablo; Basso, Luiz Augusto; Polack, Fernando P.; Čustović, Adnan; Vinolo, Marco Aurélio Ramirez; Souza, Ana Paula Duarte de

doi:10.1016/j.ebiom.2022.103891

Cited by 43 publications

(36 citation statements)

References 60 publications

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“…Alteration on the lung microbiota have been described in many respiratory diseases ( 26 , 27 ); also, the use of lung microbiota components and administration direct into the airways have been proposed to be protective against respiratory infections ( 28 , 29 ). Very recently our group showed that acetate treatment delivered directly into the airways protects against RSV infection through improvement of antiviral response modulated by RIG-I ( 30 ). Considering acetate is not a drug used in human, in the present study, we asked if a commercial product currently used orally to prevent recurrent RTIs could confer identical protection against RSV.…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…The severity of bronchiolitis was associated with specific bacterial profiles: length of hospitalization was positively associated with the family Bacteriodaceae . Furthermore, mice treated intranasally with acetate presented decreased viral load and increased expression of type 1 IFN ( Ifnb ) and retinoic acid-inducible gene I ( Rigi ) in the lung and was confirmed using in vitro analysis in A549 cells ( 97 ). Together, these studies highlight the importance of diet, gut microbiome, and microbiome-derived metabolites, especially SCFA, in controlling immune responses to RSV infection.…”

Section: Early-life Gut Microbiome Composition In Health and Diseasesmentioning

confidence: 87%

Early-Life Lung and Gut Microbiota Development and Respiratory Syncytial Virus Infection

et al. 2022

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Several environmental factors can influence the development and establishment of the early-life microbiota. For example, exposure to different environmental factors from birth to childhood will shape the lung and gut microbiota and the development of the immune system, which will impact respiratory tract infection and widespread disease occurrence during infancy and later in life. Respiratory syncytial virus (RSV) infects most infants by the age of two and is the primary cause of bronchiolitis in children worldwide. Approximately a third of infants hospitalized with bronchiolitis develop asthma later in life. However, it is unclear what factors increase susceptibility to severe RSV-bronchiolitis and the subsequent asthma development. In recent years, the role of the gut and lung microbiota in airway diseases has received increased interest, and more studies have focused on this field. Different epidemiological studies and experimental animal models have associated early-life gut microbiota dysbiosis with an increased risk of lung disease later in life. This work will review published evidence that correlated environmental factors that affect the early-life microbiota composition and their role in developing severe RSV infection.

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“…Similarly, acetate administration induced interferon-β and subsequent antiviral responses in the lung through FFAR-2 and IFNAR signaling pathways, which resulted in protection against respiratory syncytial virus (RSV) in mice ( 67 ). Acetate also induces protection in mice against human clinical isolates of RSV, which was dependent on the expression of the viral sensor retinoic-acid inducible gene I (RIG-I) ( 68 ). Furthermore, pre-treatment of human pulmonary cells and nasopharyngeal aspirate cells with acetate is protective against infection with the same RSV isolates increasing the expression of the RIG-I and interferon-stimulated genes ( 68 ).…”

Section: Beneficial Roles Of Scfa and Microbiota In Lung Homeostasis ...mentioning

confidence: 99%

“…Acetate also induces protection in mice against human clinical isolates of RSV, which was dependent on the expression of the viral sensor retinoic-acid inducible gene I (RIG-I) ( 68 ). Furthermore, pre-treatment of human pulmonary cells and nasopharyngeal aspirate cells with acetate is protective against infection with the same RSV isolates increasing the expression of the RIG-I and interferon-stimulated genes ( 68 ). In the context of bacterial pneumonia, the gut microbiota and derived metabolites may play protective effects as depletion of the gut microbiota causes increased susceptibility to Streptococcus pneumoniae infection, and alveolar macrophages exhibit diminished phagocytic activity ( 69 ).…”

Section: Beneficial Roles Of Scfa and Microbiota In Lung Homeostasis ...mentioning

confidence: 99%

“…This is consistent with data indicating that a diet-imposed weight loss recapitulates in part the changes in gut microbiota and reduction in SCFA observed during IAV infection ( 93 ), supporting the idea that reduced food consumption during viral infection may alter the gut microbiota and derived metabolites. Moreover, alterations in the gut microbiota correlate with disease severity in children with RSV bronchiolitis whereas patients with milder symptoms exhibit higher levels of acetate in the stool ( 68 , 101 ), suggesting that the composition of the microbiota and SCFA may confer protection against RSV infection in humans. It is still unclear whether these changes in the human microbiota during RSV infection are due to the inappetence reported in mice or other alternative mechanisms.…”

Section: Distal Effects Of Viral Lung Infectionmentioning

confidence: 99%

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Distal Consequences of Mucosal Infections in Intestinal and Lung Inflammation

et al. 2022

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Infectious diseases are one of the leading causes of morbidity and mortality worldwide, affecting high-risk populations such as children and the elderly. Pathogens usually activate local immune responses at the site of infection, resulting in both protective and inflammatory responses, which may lead to local changes in the microbiota, metabolites, and the cytokine environment. Although some pathogens can disseminate and cause systemic disease, increasing evidence suggests that local infections can affect tissues not directly invaded. In particular, diseases occurring at distal mucosal barriers such as the lung and the intestine seem to be linked, as shown by epidemiological studies in humans. These mucosal barriers have bidirectional interactions based mainly on multiple signals derived from the microbiota, which has been termed as the gut-lung axis. However, the effects observed in such distal places are still incompletely understood. Most of the current research focuses on the systemic impact of changes in microbiota and bacterial metabolites during infection, which could further modulate immune responses at distal tissue sites. Here, we describe how the gut microbiota and associated metabolites play key roles in maintaining local homeostasis and preventing enteric infection by direct and indirect mechanisms. Subsequently, we discuss recent murine and human studies linking infectious diseases with changes occurring at distal mucosal barriers, with particular emphasis on bacterial and viral infections affecting the lung and the gastrointestinal tract. Further, we discuss the potential mechanisms by which pathogens may cause such effects, promoting either protection or susceptibility to secondary infection.

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Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis

Cited by 43 publications

References 60 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

Early-Life Lung and Gut Microbiota Development and Respiratory Syncytial Virus Infection

Distal Consequences of Mucosal Infections in Intestinal and Lung Inflammation

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