Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation

Erp, Elisabeth A. van; Lakerveld, Anke J.; Graaf, Erik de; Larsen, Mads Delbo; Schepp, Rutger M.; Ederveen, Agnes L. Hipgrave; Ahout, Inge M. L.; Haan, Cornelis A. M. de; Wuhrer, Manfred; Luytjes, Willem; Ferwerda, Gerben; Vidarsson, Gestur; Kasteren, Puck B. van

doi:10.1101/750141

Cited by 14 publications

(18 citation statements)

References 62 publications

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“…When these virus-specific antibodies are not able to completely prevent infection, as often appears to be the case, they might still be able to mitigate the development of severe disease, for example, via the recruitment and activation of (innate) immune cells through Fc-mediated interactions (for reviews, see references 11 and 20 ). We have recently shown that, in infants, the capacity of RSV-specific antibodies to activate natural killer cells might contribute to protection from severe disease ( 21 ). In contrast, these antibodies potentially also contribute to the development of severe disease, in a process referred to as antibody-dependent enhancement (ADE) of infection and/or inflammation.…”

Section: Discussionmentioning

confidence: 99%

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

Lakerveld

Imholz

et al. 2020

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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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Section: Discussionmentioning

confidence: 99%

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

Lakerveld

Imholz

et al. 2020

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“…Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease, and is the leading cause for mortality in infants and the elderly [ 32 , 77 ]. Infection is characterised by airway obstruction, runny nose, shortness of breath, wheezing, hypoxia and in severe cases, pneumonia and bronchiolitis [ 78 ].…”

Section: Viral Infection Immune Dysregulationmentioning

confidence: 99%

Natural Killer Cell Dysfunction and Its Role in COVID-19

Eeden

Khan

Osman

et al. 2020

IJMS

152

132

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When facing an acute viral infection, our immune systems need to function with finite precision to enable the elimination of the pathogen, whilst protecting our bodies from immune-related damage. In many instances however this “perfect balance” is not achieved, factors such as ageing, cancer, autoimmunity and cardiovascular disease all skew the immune response which is then further distorted by viral infection. In SARS-CoV-2, although the vast majority of COVID-19 cases are mild, as of 24 August 2020, over 800,000 people have died, many from the severe inflammatory cytokine release resulting in extreme clinical manifestations such as acute respiratory distress syndrome (ARDS) and hemophagocytic lymphohistiocytosis (HLH). Severe complications are more common in elderly patients and patients with cardiovascular diseases. Natural killer (NK) cells play a critical role in modulating the immune response and in both of these patient groups, NK cell effector functions are blunted. Preliminary studies in COVID-19 patients with severe disease suggests a reduction in NK cell number and function, resulting in decreased clearance of infected and activated cells, and unchecked elevation of tissue-damaging inflammation markers. SARS-CoV-2 infection skews the immune response towards an overwhelmingly inflammatory phenotype. Restoration of NK cell effector functions has the potential to correct the delicate immune balance required to effectively overcome SARS-CoV-2 infection.

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“…The hRSV infection of both neonate and adult NK cells has recently been reported [ 233 ]. NK cells are poorly susceptible to hRSV infection, but the Ig-coating of hRSV greatly enhances the infection [ 233 ], suggesting yet again a possible role of the Fc receptors in the hRSV infection of immune cells. Moreover, hRSV-infected NK cells secrete higher amounts of IFN-γ than non-infected NK cells, while perforin secretion remains unaltered [ 233 ].…”

Section: Differential Regulation Of the Innate Immune Response By mentioning

confidence: 99%

“…NK cells are poorly susceptible to hRSV infection, but the Ig-coating of hRSV greatly enhances the infection [ 233 ], suggesting yet again a possible role of the Fc receptors in the hRSV infection of immune cells. Moreover, hRSV-infected NK cells secrete higher amounts of IFN-γ than non-infected NK cells, while perforin secretion remains unaltered [ 233 ]. Thus, the hRSV infection of NK cells possibly leads to a worsening of the respiratory symptoms caused by hRSV through IFN-γ-mediated pulmonary inflammation.…”

Section: Differential Regulation Of the Innate Immune Response By mentioning

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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Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation

Cited by 14 publications

References 62 publications

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

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

Natural Killer Cell Dysfunction and Its Role in COVID-19

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

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