Infant Viral Respiratory Infection Nasal Immune-Response Patterns and Their Association with Subsequent Childhood Recurrent Wheeze

Abstract

Distinct immune-response clusters during infant RSV infection and their association with risk of recurrent wheeze provide insights into the risk factors for and mechanisms of asthma development.

Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze

“…However, it has been shown that lower blood TNF‐α levels in infants with RSV bronchiolitis were associated with greater disease severity and a longer hospital stay . Our finding is consistent with the study by Turi et al evaluating nasal immune response phenotypes in infants with RSV infection in which they demonstrated low non‐IFN antiviral immune response, including TNF‐α, as significantly associated with recurrent wheezing in the first and second‐year following RSV infection. In the upper airways, a decrease in IL‐10 potentiates an increase in the TNF‐α response which controls the viral infection .…”

“…Although it is known that infants with severe RSV bronchiolitis have increased risks of recurrent wheezing and asthma in later life, previous literature on roles of innate and adaptive cytokines in the pathogenesis of subsequent wheeze following acute severe RSV bronchiolitis have been limited. 9 In our study, we have demonstrated impaired T A B L E 2 Peripheral blood CD4+CD25 hi Foxp3 hi cells and granzyme B expression and cytokine production from CD3/CD46-activated and CD3/CD28-activated CD4+ cells during severe RSV bronchiolitis in infancy by wheezing outcome Note: Data were subtracted from negative control conditions (PBS) and negative data were adjusted to zero, then log-transformed for statistical analysis. Abbreviations: IFN-γ, interferon-γ; IL, Interleukin; TNF-α, tumor necrosis factor-α.…”

“…27 A recent birth cohort study by Turi, et al have demonstrated infants who are at increased risks for recurrent wheeze in the first and second year following acute RSV infection had a unique pattern of nasal immune response characterized by lower non-IFN antiviral immune-response mediators including TNF-α and higher type-2 and type-17 cytokines. 9 TNF-α is a proinflammatory cytokine that plays roles in neutrophil and eosinophil recruitment to the airway. 28 Higher TNF-α levels in airway secretions have been observed in mice and human with RSV infection.…”

“…However, wheezing is a common outcome used in a number of studies as the majority of these wheezing episodes may not require medical attention. 9,47 Due to the limitation of blood that we can draw from infants, we did not measure the plasma cytokines in our subjects to determine the correlation with the in vitro CD4+ functional measures and did not have an adequate data to provide additional insights into the kinetics of these cytokines. The limited volume of blood in infants also prevented absolute cell counts from being determined.…”

“…[6][7][8] A recent study demonstrated that higher Th2 and Th17 cytokine levels in nasal wash samples obtained during acute RSV bronchiolitis were associated with recurrent wheezing at age one and 2 years. 9 As Foxp3+ regulatory T cells (Tregs) play an important role in maintaining the homeostasis of the immune system, 10,11 as well as limiting the inflammatory response in the lungs during the acute phase of RSV bronchiolitis, [12][13][14] we hypothesized that the frequency of circulating Tregs might differ in those children subsequently developing recurrent wheezing. It has been demonstrated that infants hospitalized with severe RSV bronchiolitis have a reduction in circulating Tregs, though subsequent outcomes are unknown.…”