title: Altered Treg and cytokine responses in RSV-infected infants.
abstract: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in children under 1 y of age in the USA. The host immune response is believed to contribute to RSV-induced disease. We hypothesize that severe RSV infection in infants is mediated by insufficient regulation of the host immune response of regulatory T cells (Tregs) resulting in immunopathology.
  
  
  
  Blood and nasal aspirates from 23 RSV-infected and 17 control infants under 1 y of age were collected. Treg frequencies were determined by flow cytometry from peripheral blood mononuclear cells. Analysis of 24 cytokines was measured by multiplex assay on nasal aspirates.
  
  
  
  We demonstrate that the frequency of activated Tregs is significantly reduced in the peripheral blood of RSV-infected infants compared with age-matched controls. Surprisingly, T helper (Th)17 related cytokines including interleukin (IL)-1β, IL-17A, and IL-23 were associated with a reduction in clinical symptoms of respiratory distress. In addition, the amount of IL-33 protein in nasal washes, a cytokine important in maintaining Treg homeostasis in mucosal tissues, was decreased in RSV-infected children.
  
  
  
  These results suggest that decreased Treg numbers and an inability to properly control the host inflammatory response results in severe RSV infection.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa.
authors.forename: Allison F
authors.initials: AF
authors.lastname: Christiaansen
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Syed
authors.affiliation: Institute for Clinical and Translational Science, University of Iowa, Iowa City, Iowa.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Ten Eyck
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Hartwig
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Durairaj
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors.forename: Sameer S
authors.initials: SS
authors.lastname: Kamath
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa.|Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa.|Department of Pathology, University of Iowa, Iowa City, Iowa.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Varga
mesh_terms: D001988:Bronchiolitis / Q000821:virology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D053760:Interleukin-23 Subunit p19 / Q000097:blood; D000067596:Interleukin-33 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology; D011014:Pneumonia / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000097:blood / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; C508717:IL17A protein, human; C508840:IL23A protein, human; C506536:IL33 protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D053760:Interleukin-23 Subunit p19; D000067596:Interleukin-33