Airway Epithelial Derived Cytokines and Chemokines and Their Role in the Immune Response to Respiratory Syncytial Virus Infection

Glaser, Lena; Coulter, Patricia; Shields, Michael; Touzelet, Olivier; Power, Ultan F.; Broadbent, Lindsay

doi:10.3390/pathogens8030106

Cited by 59 publications

(62 citation statements)

References 154 publications

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“…It is now understood that respiratory cilia share chemosensory abilities once thought unique to primary cilia, long known to be involved in chemosensation, signal transduction, and regulation of cellular growth (51,87,122,146,170). Studies have also shown possible involvement of cilia in lung repair processes (148,155) and in regulating cytokine and antimicrobial production (11,56,131), thus suggesting an even greater involvement of these organelles in lung function than initially thought. Studies by our group and others have shown that airway cilia express members of the bitter taste family of receptors (T2Rs) that may hold functional importance in airway innate immunity against bacterial infections by driving innate immune defenses in response to bacterial antigens (52,65,113,170).…”

Section: Respiratory Cilia: Structure Function and Expressionmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

128

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Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens including viruses, bacteria and fungi have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections is still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immuno-regulatory roles during infection will also be discussed.

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Section: Respiratory Cilia: Structure Function and Expressionmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

128

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“…The respiratory epithelium is an important driver of the immune response against respiratory viruses, as these cells are implicated in the secretion of large quantities of chemokines upon infection. This will attract immune cells to the site of infection, as well as other various cytokines that modulate the immune response [ 267 ].…”

Section: Role Of the Respiratory Epithelium During The Immune Respmentioning

confidence: 99%

“…For hRSV, epithelial cells have been seen to contribute to the promotion of local inflammation and angiogenesis, the recruitment of various inflammatory cell types, and the development of a harmful T H 2 adaptive immune response. Many of these studies are based on in vitro models, and we only discuss the secretion of cytokines that have been observed in at least one type of human primary cell culture [ 118 , 230 , 247 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 , 289 , 290 , 291 , 292 , 293 , 294 , 295 , 296 , 297 , 298 ].…”

Section: Role Of the Respiratory Epithelium During The Immune Respmentioning

confidence: 99%

Innate Immune Components That Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections

Andrade

Pacheco

Gálvez

et al. 2020

Viruses

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The human respiratory syncytial virus (hRSV) and human Metapneumovirus (hMPV) are two of the leading etiological agents of acute lower respiratory tract infections, which constitute the main cause of mortality in infants. However, there are currently approved vaccines for neither hRSV nor hMPV. Moreover, despite the similarity between the pathology caused by both viruses, the immune response elicited by the host is different in each case. In this review, we discuss how dendritic cells, alveolar macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid cells, and the complement system regulate both pathogenesis and the resolution of hRSV and hMPV infections. The roles that these cells play during infections by either of these viruses will help us to better understand the illnesses they cause. We also discuss several controversial findings, relative to some of these innate immune components. To better understand the inflammation in the lungs, the role of the respiratory epithelium in the recruitment of innate immune cells is briefly discussed. Finally, we review the main prophylactic strategies and current vaccine candidates against both hRSV and hMPV.

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“…RSV infection induces upregulation of a variety of cytokines in the nasal mucosa of older adults. Mucosal cytokine production plays an important role in modulation of the (protective or pathogenic) immune response to RSV (17). However, few data are available on the local cytokine response in the older adult population specifically (9).…”

Section: Fig 2 Serologic Analyses Of Rsv-infected Participants and Comentioning

confidence: 99%

Antibody and Local Cytokine Response to Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults

Lakerveld

Imholz

et al. 2020

mSphere

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Respiratory syncytial virus (RSV) is increasingly recognized for causing severe morbidity and mortality in older adults, but there are few studies on the RSV-induced immune response in this population. Information on the immunological processes at play during RSV infection in specific risk groups is essential for the rational and targeted design of novel vaccines and therapeutics. Here, we assessed the antibody and local cytokine response to RSV infection in community-dwelling older adults (≥60 years of age). During three winters, serum and nasopharyngeal swab samples were collected from study participants during acute respiratory infection and recovery. RSV IgG enzyme-linked immunosorbent assays (ELISA) and virus neutralization assays were performed on serum samples from RSV-infected individuals (n = 41) and controls (n = 563 and n = 197, respectively). Nasal RSV IgA and cytokine concentrations were determined using multiplex immunoassays in a subset of participants. An in vitro model of differentiated primary bronchial epithelial cells was used to assess RSV-induced cytokine responses over time. A statistically significant increase in serum neutralization titers and IgG concentrations was observed in RSV-infected participants compared to controls. During acute RSV infection, a statistically significant local upregulation of beta interferon (IFN-β), IFN-λ1, IFN-γ, interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), IL-6, IL-10, CXCL8, and CXCL10 was found. IFN-β, IFN-λ1, CXCL8, and CXCL10 were also upregulated in the epithelial model upon RSV infection. In conclusion, this study provides novel insights into the basic immune response to RSV infection in an important and understudied risk population, providing leads for future studies that are essential for the prevention and treatment of severe RSV disease in older adults. IMPORTANCE Respiratory syncytial virus (RSV) can cause severe morbidity and mortality in certain risk groups, especially infants and older adults. Currently no (prophylactic) treatment is available, except for a partially effective yet highly expensive monoclonal antibody. RSV therefore remains a major public health concern. To allow targeted development of novel vaccines and therapeutics, it is of great importance to understand the immunological mechanisms that underlie (protection from) severe disease in specific risk populations. Since most RSV-related studies focus on infants, there are only very limited data available concerning the response to RSV in the elderly population. Therefore, in this study, RSV-induced antibody responses and local cytokine secretion were assessed in community-dwelling older adults. These data provide novel insights that will benefit ongoing efforts to design safe and effective prevention and treatment strategies for RSV in an understudied risk group.

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Airway Epithelial Derived Cytokines and Chemokines and Their Role in the Immune Response to Respiratory Syncytial Virus Infection

Cited by 59 publications

References 154 publications

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Innate Immune Components That Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections

Antibody and Local Cytokine Response to Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults

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