title: Interferon α-Enhanced Clearance of Group A Streptococcus Despite Neutropenia.
abstract: Neutrophils and monocytes are crucial for controlling bacterial infections. More-frequent bacterial infections are accordingly encountered in neutropenic patients undergoing chemotherapy. This is not the case for pegylated interferon α (IFN-α)-induced neutropenia. We hypothesized that IFN-α induces a compensatory innate antibacterial state that prevents bacterial infections despite the neutropenia.
  
  
  
  To investigate whether patients with hepatitis C virus infection treated with IFN-α killed group A Streptococcus (GAS) better than before initiating therapy, whole blood was used to perform ex vivo GAS killing assays before, during, and after IFN-α therapy.
  
  
  
  We found that IFN-α therapy enhanced GAS killing in whole blood ex vivo despite the decreased neutrophil and monocyte numbers during IFN-α therapy. IFN-α also boosted neutrophil- and monocyte-mediated GAS killing in vitro. Underlying mechanisms included increased production of the antibacterial properdin, a regulator of the complement activation, as well as reactive oxygen species.
  
  
  
  These findings help to explain the rather discrepant facts of neutropenia but preserved antibacterial immune defenses in patients treated with IFN-α.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchiyama
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Nadia
authors.initials: N
authors.lastname: Keller
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Erika
authors.initials: E
authors.lastname: Schlaepfer
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Christina
authors.initials: C
authors.lastname: Grube
authors.affiliation: Division of Surgical Intensive Care, University Hospital Zurich, University of Zurich, Switzerland.
authors.forename: Reto A
authors.initials: RA
authors.lastname: Schuepbach
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Speck
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Annelies S
authors.initials: AS
authors.lastname: Zinkernagel
mesh_terms: D001770:Blood Bactericidal Activity; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000378:metabolism*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D050296:Microbial Viability; D009503:Neutropenia; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000502:physiology
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha
keywords: Streptococcus pyogenes; interferon α; monocytes; neutropenia; properdin