title: Human norovirus infection and the acute serum cytokine response.
abstract: Noroviruses (NoV) are the most common cause of epidemic gastroenteritis worldwide. The acute immune response to NoV in humans is poorly understood, hindering research on prevention and treatment. To elucidate the acute immune response and test for cytokine predictors of susceptibility to infection, serum samples from two human NoV challenge studies were tested for 16 cytokines. Subjects who became infected (n = 26) were age-matched with subjects who remained uninfected following NoV challenge (n = 26). Samples were tested from prechallenge and days 1-4 post-challenge. Cytokine responses were compared between infected and uninfected groups. Overall, infected individuals exhibited an elevation in T helper type 1 (Th1) and Th2 cytokines, as well as chemokines interleukin (IL)-8 and monocyte chemoattractant protein (MCP-1), compared to uninfected individuals (all P < 0.05). Most cytokines peaked on day 2 post-challenge in infected subjects, and tumour necrosis factor (TNF)-α, IL-8, and IL-10 remained elevated to day 3. The only cytokine elevated significantly among infected subjects to day 4 post-challenge was IL-10 (P = 0.021). Prechallenge cytokine concentrations were not predictive of infection status post-challenge. There were no significant changes in serum cytokines among NoV-challenged subjects who remained uninfected. These results suggest that NoV infection elicits a Th1-type response, with some Th2 activation. Persistent elevation of IL-10 among infected subjects is consistent with activation of adaptive immune responses, such as B cell expansion, as well as down-regulation of Th1 cytokines. This study presents the first comprehensive description of the acute cytokine response to GI.1 NoV in humans.
authors.affiliation: Department of Epidemiology, Emory University, Atlanta, GA, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Newman
authors.affiliation: Department of Epidemiology, Emory University, Atlanta, GA, USA.|Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Moe
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: A E
authors.identifier: http://orcid.org/0000-0002-6928-668X
authors.initials: AE
authors.lastname: Kirby
authors.affiliation: Department of Epidemiology, Emory University, Atlanta, GA, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Flanders
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Parkos
authors.affiliation: Department of Epidemiology, Emory University, Atlanta, GA, USA.|Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Leon
mesh_terms: D000328:Adult; D017250:Caliciviridae Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D018932:Chemokine CCL2 / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005243:Feces / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000097:blood / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D008297:Male; D029322:Norovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D016209:Interleukin-8; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: adaptive immunity; caliciviruses; innate immunity