Invasion and survival strategies ofAnaplasma phagocytophilum

Abstract

SummaryAnaplasma phagocytophilum is an aetiological agent of human granulocytic ehrlichiosis, an emerging tickborne zoonosis in the United States and Europe. This obligate intracellular bacterium is unique in that it colonizes polymorphonuclear leucocytes (neutrophils). Neutrophils are key players in innate immunity. These short-lived phagocytes ingest invading microorganisms and destroy them by various means, which include fusing the bacteria-containing phagosome with acidic lysosomes as well as directing toxic oxidative and proteolytic compounds into the phagosomal lumen. Its tropism for neutrophils indicates that A. phagocytophilum uses strategies for evading and/ or neutralizing these microbicidal activities. This review focuses on some of the mechanisms that A. phagocytophilum uses for neutrophil adhesion, surviving within the hostile intracellular environment of its host neutrophil and for effectively disseminating to naïve host cells.

Infection with Anaplasma phagocytophilum Activates the Phosphatidylinositol 3-Kinase/Akt and NF-κB Survival Pathways in Neutrophil Granulocytes

“…Previous studies concerning this phenomenon focused on the effect of the infection on the executionary apoptotic cascade, showing that A. phagocytophilum inhibits neutrophil apoptosis by modulating the extrinsic as well as the intrinsic pathway of apoptosis (9). However, it is still poorly understood which signals regulate this process.…”

Infection of Ixodes spp. tick cells with different Anaplasma phagocytophilum isolates induces the inhibition of apoptotic cell death

“…A. phagocytophilum is able to inhibit host cell apoptosis pathways as a mechanism to improve its survival and multiplication inside the host cell (Rikihisa, 2010). In vertebrates, the pathogen has the ability to delay host cell apoptosis by activation of an anti-apoptotic cascade since this is crucial for its intracellular survival and reproduction in the neutrophils whose life cycle is normally short (Carlyon and Fikrig, 2003;Galindo et al, 2008). Different studies have shown that A. phagocytophilum infection upregulates the expression of anti-apoptotic blc-2 genes, blocks cell surface fatty acid synthase (FAS) clustering during spontaneous neutrophil apoptosis and inhibits cleavage of pro-Caspase 8 and Caspase 8 activation as well as secretion Anaplasma translocated substrate-1 (Ats-1) preventing mitochondrial response to apoptotic signals (Niu et al, 2010;Rikihisa, 2010).…”

Anaplasma phagocytophilumUtilizes Multiple Host Evasion Mechanisms To Thwart NADPH Oxidase-Mediated Killing during Neutrophil Infection

“…Human anaplasmosis (formerly called human granulocytic ehrlichiosis) is an emerging vector-borne infection in the United States and Europe (8,10,15). The causative agent is Anaplasma phagocytophilum, an obligate intracellular bacterium that naturally cycles among ticks of the Ixodes ricinus complex and mammalian hosts (8,15,16).…”

“…The causative agent is Anaplasma phagocytophilum, an obligate intracellular bacterium that naturally cycles among ticks of the Ixodes ricinus complex and mammalian hosts (8,15,16). Humans are occasional inadvertent hosts.…”

“…The hallmark manifestation, however, is A. phagocytophilum colonization of polymorphonuclear leukocytes. Severe, potentially fatal complications can result, including prolonged fever, shock, pneumonitis, and increased susceptibility to opportunistic infections (8,15).…”