title: A systemic neutrophil response precedes robust CD8(+) T-cell activation during natural respiratory syncytial virus infection in infants.
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 the viral 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.
authors.affiliation: Department of Pediatrics, The Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors.forename: Michaël V
authors.initials: MV
authors.lastname: Lukens
authors.forename: Alma C
authors.initials: AC
authors.lastname: van de Pol
authors.forename: Frank E J
authors.initials: FE
authors.lastname: Coenjaerts
authors.forename: Nicolaas J G
authors.initials: NJ
authors.lastname: Jansen
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kamp
authors.forename: Jan L L
authors.initials: JL
authors.lastname: Kimpen
authors.forename: John W A
authors.initials: JW
authors.lastname: Rossen
authors.forename: Laurien H
authors.initials: LH
authors.lastname: Ulfman
authors.forename: Carline E A
authors.initials: CE
authors.lastname: Tacke
authors.forename: Marco C
authors.initials: MC
authors.lastname: Viveen
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
authors.forename: Tom F W
authors.initials: TF
authors.lastname: Wolfs
authors.forename: Grada M
authors.initials: GM
authors.lastname: van Bleek
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D012367:RNA, Viral / Q000378:metabolism; D012121:Respiration, Artificial; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000503:physiopathology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D012720:Severity of Illness Index; D019562:Viral Load
chemical_list: D012367:RNA, Viral