Open AccessImpairment of Gamma Interferon Signaling in Human Neutrophils Infected withAnaplasma phagocytophilum
Author(s) -
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
Publication year - 2010
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01005-09
Subject(s) - anaplasma phagocytophilum , biology , interferon gamma , microbiology and biotechnology , chemokine , intracellular parasite , anaplasma , intracellular , secretion , interferon , immunology , virology , cytokine , inflammation , borrelia burgdorferi , antibody , biochemistry , tick
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-gamma)-deficient mice suggested a major role of IFN-gamma in the control of A. phagocytophilum. Here we investigated whether infection of human PMN with A. phagocytophilum impairs IFN-gamma signaling thus facilitating intracellular survival of the bacterium. The secretion of the IFN-gamma-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-gamma receptor alpha-chain CD119, diminished the IFN-gamma-induced phosphorylation of STAT1, and enhanced the expression of SOCS1 and SOCS3 in PMN. Since IFN-gamma activates various antibacterial effector mechanisms of PMN, the impaired IFN-gamma signaling in infected cells likely contributes to the survival of A. phagocytophilum inside PMN and to HGA disease development.