IAI Accepts, published online ahead of print on 26 October 2009

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Infect. Immun. doi:10.1128/IAI.01005-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Impairment of 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-Haerer, J. Stephen Dumler, Friederike D. von Loewenich, Werner Solbach, and Tamás Laskay^*

Institute of Medical Microbiology and Hygiene, University of Luebeck, Germany; Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, University Clinic of Erlangen, Erlangen, Germany; Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany

^* To whom correspondence should be addressed. Email: Tamas.Laskay{at}uk-sh.de.

Anaplasma (A.) 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 IFN--deficient mice suggested a major role of IFN- in the control of A. phagocytophilum. Here we investigated whether infection of human PMN with A. phagocytophilum impairs IFN- signaling thus facilitating intracellular survival of the bacterium. The secretion of the IFN--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- receptor -chain CD119, diminished the IFN--induced phosphorylation of STAT1, and enhanced the expression of SOCS1 and SOCS3 in PMN. Since IFN- activates various antibacterial effector mechanisms of PMN, the impaired IFN- signaling in infected cells likely contributes to the survival of A. phagocytophilum inside PMN and to HGA disease development.