Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection

Contribution: Visualization

International audience

anglais. <em>Anaplasma phagocytophilumi</em>s an emerging zoonotic pathogen that causes human and animalgranulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacteriumevolved to use common strategies to establish infection in both vertebrate hosts and tick vectors.Herein, we discuss the different strategies used by the pathogen to modulate cell apoptosis andestablish infection in host cells. In vertebrate neutrophils and human promyelocytic cells HL-60,both pro-apoptotic and anti-apoptotic factors have been reported. Tissue-specific differences intick response to infection and differential regulation of apoptosis pathways have been observed inadult female midguts and salivary glands in response to infection withA. <em>phagocytophilum</em>.In tickmidguts, pathogen inhibits apoptosis through the Janus kinase/signal transducers and activatorsof transcription (JAK/STAT) pathway, while in salivary glands, the intrinsic apoptosis pathwaysis inhibited but tick cells respond with the activation of the extrinsic apoptosis pathway. InIxodesscapularisISE6 cells, bacterial infection down-regulates mitochondrial porin and manipulates proteinprocessing in the endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and facilitateinfection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis appears to be regulated by lowercaspase levels. These results suggest thatA. p<em>hagocytophilum</em> uses different mechanisms to inhibitapoptosis for infection of both vertebrate and invertebrate hosts.