Infection with Anaplasma phagocytophilum activates the phosphatidylinositol 3-Kinase/Akt and NF-κB survival pathways in neutrophil granulocytes

Arup Sarkar, Lars Hellberg, Asima Bhattacharyya, Martina Behnen, Keqing Wang, Janet M. Lord, Sonja Möller, Maja Kohler, Werner Solbach, Tamás Laskay

Research output: Contribution to journalArticle

Abstract

Anaplasma phagocytophilum, a Gram-negative, obligate intracellular bacterium infects primarily neutrophil granulocytes. Infection with A. phagocytophilum leads to inhibition of neutrophil apoptosis and consequently contributes to the longevity of the host cells. Previous studies demonstrated that the infection inhibits the executionary apoptotic machinery in neutrophils. However, little attempt has been made to explore which survival signals are modulated by the pathogen. The aim of the present study was to clarify whether the phosphatidylinositol 3-kinase (PI3K)/Akt and NF-?B signaling pathways, which are considered as important survival pathways in neutrophils, are involved in A. phagocytophilum-induced apoptosis delay. Our data show that infection of neutrophils with A. phagocytophilum activates the PI3K/Akt pathway and suggest that this pathway, which in turn maintains the expression of the antiapoptotic protein Mcl-1, contributes to the infection-induced apoptosis delay. In addition, the PI3K/Akt pathway is involved in the activation of NF-?B in A. phagocytophilum-infected neutrophils. Activation of NF-?B leads to the release of interleukin-8 (IL-8) from infected neutrophils, which, in an autocrine manner, delays neutrophil apoptosis. In addition, enhanced expression of the antiapoptotic protein cIAP2 was observed in A. phagocytophilum-infected neutrophils. Taken together, the data indicate that upstream of the apoptotic cascade, signaling via the PI3K/Akt pathway plays a major role for apoptosis delay in A. phagocytophilum-infected neutrophils.
Original languageEnglish
Pages (from-to)1615-1623
Number of pages9
JournalInfection and Immunity
Volume80
Issue number4
Early online date17 Jan 2012
DOIs
Publication statusPublished - Apr 2012

Bibliographical note

Open access

Keywords

  • NF-kappa B
  • apoptosis
  • Humans
  • anaplasma phagocytophilum
  • proto-oncogene proteins c-akt
  • inhibitor of apoptosis proteins
  • proto-oncogene proteins c-bcl-2
  • neutrophils
  • cultured cells
  • interleukin-8
  • phagocytosis
  • phosphatidylinositol 3-Kinase
  • signal transduction

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