Severe Human Lower Respiratory Tract Illness Caused by Respiratory Syncytial Virus and Influenza Virus Is Characterized by the Absence of Pulmonary Cytotoxic Lymphocyte Responses

Welliver, Timothy P.; Garofalo, Roberto P.; Hosakote, Yashoda Madaiah; Hintz, Karen H.; Avendaño, Luis F.; Sánchez, Katherine; Velozo, Luis; Jafri, Hasan S.; Chávez-Bueno, Susana; Ogra, Pearay L.; McKinney, Lu Ann; Reed, Jennifer L.; Welliver, Robert C.

doi:10.1086/512615

Cited by 374 publications

(452 citation statements)

References 47 publications

Supporting

Mentioning

410

Contrasting

Unclassified

Order By: Relevance

“…We hypothesised that children with severe bronchiolitis had a defect in the APC-IL-15-NK cell axis that prevented the development of a competent innate response to respiratory viral infection. This might account for the paucity of NK cells in lung tissue seen at autopsy studies of children who died from severe viral bronchiolitis [32]. Lymphocyte phenotyping by flow cytometry revealed a significant drop in the relative percentage of NK cells seen in the peripheral blood among children with bronchiolitis.…”

Section: Discussionmentioning

confidence: 98%

Interleukin-15 is associated with disease severity in viral bronchiolitis

et al. 2015

View full text Add to dashboard Cite

Disease severity in viral bronchiolitis in infancy is difficult to predict and has been linked to host innate immunity. The study aimed to investigate the innate cytokine interleukin-15 (IL-15) as a marker of disease severity.A prospective single-centre observational study was conducted in a university-affiliated paediatric teaching hospital, comparing children (0-18 months) hospitalised for viral bronchiolitis, those admitted to the paediatric intensive care unit with severe disease and healthy age-matched controls. IL-15-related parameters were compared between groups. PCR and microRNA (miRNA) sequencing was undertaken on natural killer (NK) cells collected from study participants.Samples from 88 children with viral bronchiolitis and 43 controls enrolled between 2009 and 2012 were analysed. Peripheral blood mononuclear cell (PBMC) IL-15 mRNA expression was significantly higher in those with moderate severity bronchiolitis compared with controls and those with severe disease. Serum IL-15 levels correlated with disease severity. The relative frequency of NK cells in peripheral blood was significantly reduced in participants with bronchiolitis. The NK cell miRNA transcriptome in bronchiolitis was distinct. Targets of de-regulated miRNA were differentially expressed in bronchiolitis, including JAK3, STAT5A and NFKB1 on the IL-15 signalling pathway.IL-15 is associated with disease severity in children hospitalised with viral bronchiolitis.@ERSpublications Interleukin-15 influences the host innate response and is associated with disease severity in viral bronchiolitis

show abstract

Section: Discussionmentioning

confidence: 98%

Interleukin-15 is associated with disease severity in viral bronchiolitis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Microscopic examination of bronchoalveolar lavage fluid and lung tissue from morbid mice revealed profound inflammation, most notable for recruitment of granulocytes and for severe pulmonary edema consistent with the clinical findings characteristic of acute respiratory distress syndrome (ARDS; Figure 4). Interestingly, severe inflammation, edema and recruitment of granulocytes have also been characterized in a recent series of RSV-diagnosed post-mortem samples evaluated by Welliver and colleagues [25]. PVM replication in situ results in local production of proinflammatory mediators, including MIP-1α, MIP-2, MCP-1 and IFNγ [24].…”

Section: Inflammatory Responses and Disease Severitymentioning

confidence: 89%

“…Reprinted with permission from Rosenberg HF et al [11]. [24]; RSV images reprinted with permission from Welliver TP et al, [25]. Wild type and IFNγR gene-deleted mice were vaccinated with live-attenuated PVM strain 15 (ATCC), heat-inactivated strain 15, or diluent alone and challenged with virulent strain J3666.…”

Section: Discussionmentioning

confidence: 99%

Pneumonia virus of mice: severe respiratory infection in a natural host

Rosenberg

Domachowske

2008

Immunology Letters

View full text Add to dashboard Cite

Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to the human and bovine respiratory syncytial viruses. Among the prominent features of this infection, robust replication of PVM takes place in bronchial epithelial cells in response to a minimal virus inoculum. Virus replication in situ results in local production of proinflammatory cytokines (MIP-1α, MIP-2, MCP-1 and IFNγ) and granulocyte recruitment to the lung. If left unchecked, PVM infection and the ensuing inflammatory response ultimately lead to pulmonary edema, respiratory compromise and death. In this review, we consider the recent studies using the PVM model that have provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. We also highlight several works that have elucidated acquired immune responses to this pathogen, including T cell responses and the development of humoral immunity. Finally, we consider several immunomodulatory strategies that have been used successfully to reduce morbidity and mortality when administered to PVM infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe respiratory virus infections in human subjects.

show abstract

“…59 hRSV-mediated lung pathology in mice is not completely dissected and primary reports attributed this effect to T cells, specially CD8 C T 67,68 but in humans, it has mostly been associated with a large influx of neutrophils in the lungs of patients with bronchiolitis, as well as in fatal cases of infants. [69][70][71] It is suggested that neutrophils recruitment induced by hRSV infection promote lung damage through the generation of reactive oxygen species and extracellular traps (NETs). 72,73 Nevertheless, a recent study using experimental hRSV infection of adults in which a 65% of individuals presented inflammation symptoms, has shown that the virus replicate in the lower respiratory tract, inducing cellular infiltration of CD8 C T cells to the airways.…”

Section: Both Memory Cd4mentioning

confidence: 99%

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

et al. 2016

View full text Add to dashboard Cite

Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections.In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.

show abstract

Severe Human Lower Respiratory Tract Illness Caused by Respiratory Syncytial Virus and Influenza Virus Is Characterized by the Absence of Pulmonary Cytotoxic Lymphocyte Responses

Abstract: Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.

Cited by 374 publications

References 47 publications

Interleukin-15 is associated with disease severity in viral bronchiolitis

Interleukin-15 is associated with disease severity in viral bronchiolitis

Pneumonia virus of mice: severe respiratory infection in a natural host

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

Contact Info

Product

Resources

About