Host immune responses are thought to influence disease manifestations during primary RSV infection,. Additionally, RSV-related emergency department visits for infants aged ≤ 1 year of age range from 39 to, and RSV-related office visits are 3 times as many. Although most infections are relatively mild, 1%–3% of infected infants require hospitalization, accounting for 74,000–126,000 admissions of infants aged < 1 year annually in the United States. Respiratory syncytial virus (RSV), the most important cause of respiratory tract illness in infants and young children, infects 50%–70% of infants during the first year of life. In conclusion, T cell responses to RSV in infants may not follow the canonical Th1/Th2 patterns of effector responses but include additional functions that may be unique to the neonatal period and correlate with clinical outcomes. Future work using additional markers identified in this study could reveal additional unconventional T cells responding to RSV infections in infants. Indeed, CD4+CXCL9+ cells were identified upon M-peptide stimulation by flow cytometry. Hence, based on transcriptional response, markers were chosen to validate the role of M-peptide in activation of T cells. This analysis also suggested activation of T cell response upon M-peptide stimulation. Moreover, signatures of natural RSV infections were identified from the data available in the public domain to investigate similarities between transcriptional signatures from PBMCs and upon peptide stimulation. This along with upregulation of several unconventional T cell signatures was only observed upon M-peptide stimulation. Unexpected from the ICS data, M peptide induced a response equivalent to the F-peptide and was characterized by activation of GATA2, 3, STAT3 and IRF1. To understand the cellular response using transcriptional signatures, transcription factors and cell-type specific signatures were used to investigate breadth of response across peptides. Therefore we sought an unbiased approach to identify RSV-specific immune markers using RNA-sequencing upon stimulation of infant PBMCs with overlapping peptides representing RSV antigens. Flow cytometry analysis of cellular responses using “conventional” anti-viral markers (IL2, IFN-γ, TNF, IL10 and IL4) upon RSV-peptide stimulation detected an overall low RSV response in peripheral blood. Observations of neonatal and infant T cells suggest that they may express different immune markers compared to T-cells from older children. Respiratory syncytial virus (RSV) is the most important cause of respiratory tract illness especially in young infants that develop severe disease requiring hospitalization, and accounting for 74,000–126,000 admissions in the United States (Rezaee et al., 2017 Resch, 2017).
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