Impairment of gamma interferon signaling in human neutrophils infected with Anaplasma phagocytophilum

Uta Bussmeyer, Arup Sarkar, Kirsten Broszat, Tanja Lüdemann, Sonja Möller, Ger Van Zandbergen, Christian Bogdan, Martina Behnen, J. Stephen Dumler, Friederike D. Von Loewenich, Werner Solbach, Tamás Laskay

Research output: Contribution to journalArticlepeer-review

Abstract

Anaplasma phagocytophilum, the causative agent of tick-borne human granulocytic anaplasmosis (HGA), is an intracellular bacterium which survives and multiplies inside polymorphonuclear neutrophil granulocytes (PMN). Increased bacterial burden in gamma interferon (IFN-γ)-deficient mice suggested a major role of IFN-γ in the control of A. phagocytophilum. Here we investigated whether infection of human PMN with A. phagocytophilum impairs IFN-γ signaling thus facilitating intracellular survival of the bacterium. The secretion of the IFN-γ-inducible chemokines IP-10/CXCL10 and MIG/CXCL9 was markedly inhibited in infected neutrophils. Molecular analyses revealed that, compared to uninfected PMN, A. phagocytophilum decreased the expression of the IFN-γ receptor α-chain CD119, diminished the IFN-γ-induced phosphorylation of STAT1, and enhanced the expression of SOCS1 and SOCS3 in PMN. Since IFN-γ activates various antibacterial effector mechanisms of PMN, the impaired IFN-γ signaling in infected cells likely contributes to the survival of A. phagocytophilum inside PMN and to HGA disease development.

Original languageEnglish (US)
Pages (from-to)358-363
Number of pages6
JournalInfection and immunity
Volume78
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Impairment of gamma interferon signaling in human neutrophils infected with Anaplasma phagocytophilum'. Together they form a unique fingerprint.

Cite this