A Systemic Neutrophil Response Precedes Robust CD8(+) T-Cell Activation during Natural Respiratory Syncytial Virus Infection in Infants

Michaël Lukens, Alma C. van de Pol, Frank E. J. Coenjaerts, Nicolaas J. G. Jansen, Vera M. Kamp, Jan L. L. Kimpen, John W. A. Rossen, Laurien H. Ulfman, Carline E. A. Tacke, Marco C. Viveen, Leo Koenderman, Tom F. W. Wolfs, Grada M. van Bleek*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    91 Citations (Scopus)

    Abstract

    Severe primary respiratory syncytial virus (RSV) infections are characterized by bronchiolitis accompanied by wheezing. Controversy exists as to whether infants suffer from virus-induced lung pathology or from excessive immune responses. Furthermore, detailed knowledge about the development of primary T-cell responses to viral infections in infants is lacking. We studied the dynamics of innate neutrophil and adaptive T-cell responses in peripheral blood in relation to theviral load and parameters of disease in infants admitted to the intensive care unit with severe RSV infection. Analysis of primary T-cell responses showed substantial CD8(+) T-cell activation, which peaked during convalescence. A strong neutrophil response, characterized by mobilization of bone marrow-derived neutrophil precursors, preceded the peak in T-cell activation. The kinetics of this neutrophil response followed the peak of clinical symptoms and the viral load with a 2- to 3-day delay. From the sequence of events, we conclude that CD8(+) T-cell responses, initiated during primary RSV infections, are unlikely to contribute to disease when it is most severe. The mobilization of precursor neutrophils might reflect the strong neutrophil influx into the airways, which is a characteristic feature during RSV infections and might be an integral pathogenic process in the disease.

    Original languageEnglish
    Pages (from-to)2374-2383
    Number of pages10
    JournalJournal of Virology
    Volume84
    Issue number5
    DOIs
    Publication statusPublished - Mar-2010

    Keywords

    • VIRAL-INFECTION
    • INFLUENZA-VIRUS
    • MONOCLONAL-ANTIBODY
    • CYTOKINE RESPONSES
    • DISEASE SEVERITY
    • IMMUNE-RESPONSE
    • YOUNG-CHILDREN
    • BRONCHIOLITIS
    • MICE
    • EFFECTOR

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