title: Innate immune responses in hepatitis C virus-exposed healthcare workers who do not develop acute infection.
abstract: Hepatitis C virus (HCV) infection typically results in chronic disease with HCV outpacing antiviral immune responses. Here we asked whether innate immune responses are induced in healthcare workers who are exposed to small amounts of HCV, but do not develop systemic infection and acute liver disease. Twelve healthcare workers with accidental percutaneous exposure to HCV-infected blood were prospectively studied for up to 6 months for phenotype and function of natural killer T (NKT) and NK cells, kinetics of serum chemokines, and vigor and specificity of HCV-specific T-cell responses. Eleven healthcare workers tested negative for HCV RNA and HCV antibodies. All but one of these aviremic cases displayed NKT cell activation, increased serum chemokines levels, and NK cell responses with increased CD122, NKp44, NKp46, and NKG2A expression, cytotoxicity (as determined by TRAIL and CD107a expression), and interferon-gamma (IFN-γ) production. This multifunctional NK cell response appeared a month earlier than in the one healthcare worker who developed high-level viremia, and it differed from the impaired IFN-γ production, which is typical for NK cells in chronic HCV infection. The magnitude of NKT cell activation and NK cell cytotoxicity correlated with the magnitude of the subsequent HCV-specific T-cell response. T-cell responses targeted nonstructural HCV sequences that require translation of viral RNA, which suggests that transient or locally contained HCV replication occurred without detectable systemic viremia.
  
  
  CONCLUSIONS
  Exposure to small amounts of HCV induces innate immune responses, which correlate with the subsequent HCV-specific T-cell response and may contribute to antiviral immunity.
authors: Liver Diseases Branch, NIDDK, National Institutes of Health, DHHS, Bethesda, MD.
authors: Jens Martin
authors: JM
authors: Werner
authors: Theo
authors: T
authors: Heller
authors: Ann Marie
authors: AM
authors: Gordon
authors: Arlene
authors: A
authors: Sheets
authors: Averell H
authors: AH
authors: Sherker
authors: Ellen
authors: E
authors: Kessler
authors: Kathleen S
authors: KS
authors: Bean
authors: M'Lou
authors: M
authors: Stevens
authors: James
authors: J
authors: Schmitt
authors: Barbara
authors: B
authors: Rehermann
mesh_terms: D000208:Acute Disease; D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D054405:Chemokine CCL3 / Q000032:analysis; D005260:Female; D006282:Health Personnel; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D053646:Interleukin-2 Receptor beta Subunit / Q000032:analysis; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology; D016273:Occupational Exposure; D011446:Prospective Studies; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis; D014766:Viremia / Q000276:immunology
chemical_list: C515429:CCL3 protein, human; D054405:Chemokine CCL3; D053646:Interleukin-2 Receptor beta Subunit; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human