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

Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved to use common strategies to establish infection in both vertebrate hosts and tick vectors. Herein, we dis...

Full description

Bibliographic Details
Main Authors: Pilar Alberdi, Pedro J. Espinosa, Alejandro Cabezas-Cruz, José de la Fuente
Format: Article
Language:English
Published: MDPI AG 2016-07-01
Series:Veterinary Sciences
Subjects:
Online Access:http://www.mdpi.com/2306-7381/3/3/15
_version_ 1819276810838343680
author Pilar Alberdi
Pedro J. Espinosa
Alejandro Cabezas-Cruz
José de la Fuente
author_facet Pilar Alberdi
Pedro J. Espinosa
Alejandro Cabezas-Cruz
José de la Fuente
author_sort Pilar Alberdi
collection DOAJ
description Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved 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 and establish 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 in tick response to infection and differential regulation of apoptosis pathways have been observed in adult female midguts and salivary glands in response to infection with A. phagocytophilum. In tick midguts, pathogen inhibits apoptosis through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, while in salivary glands, the intrinsic apoptosis pathways is inhibited but tick cells respond with the activation of the extrinsic apoptosis pathway. In Ixodes scapularis ISE6 cells, bacterial infection down-regulates mitochondrial porin and manipulates protein processing in the endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and facilitate infection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis appears to be regulated by lower caspase levels. These results suggest that A. phagocytophilum uses different mechanisms to inhibit apoptosis for infection of both vertebrate and invertebrate hosts.
first_indexed 2024-12-23T23:46:08Z
format Article
id doaj.art-68d91e6ca7664fdcb5a052d54463abab
institution Directory Open Access Journal
issn 2306-7381
language English
last_indexed 2024-12-23T23:46:08Z
publishDate 2016-07-01
publisher MDPI AG
record_format Article
series Veterinary Sciences
spelling doaj.art-68d91e6ca7664fdcb5a052d54463abab2022-12-21T17:25:31ZengMDPI AGVeterinary Sciences2306-73812016-07-01331510.3390/vetsci3030015vetsci3030015Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish InfectionPilar Alberdi0Pedro J. Espinosa1Alejandro Cabezas-Cruz2José de la Fuente3SaBio. Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ciudad Real 13005, SpainSaBio. Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ciudad Real 13005, SpainCenter for Infection and Immunity of Lille (CIIL), INSERM U1019-CNRS UMR 8204, Université Lille Nord de France, Institut Pasteur de Lille, Lille 59000, FranceSaBio. Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ciudad Real 13005, SpainAnaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved 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 and establish 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 in tick response to infection and differential regulation of apoptosis pathways have been observed in adult female midguts and salivary glands in response to infection with A. phagocytophilum. In tick midguts, pathogen inhibits apoptosis through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, while in salivary glands, the intrinsic apoptosis pathways is inhibited but tick cells respond with the activation of the extrinsic apoptosis pathway. In Ixodes scapularis ISE6 cells, bacterial infection down-regulates mitochondrial porin and manipulates protein processing in the endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and facilitate infection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis appears to be regulated by lower caspase levels. These results suggest that A. phagocytophilum uses different mechanisms to inhibit apoptosis for infection of both vertebrate and invertebrate hosts.http://www.mdpi.com/2306-7381/3/3/15tickAnaplasmaapoptosisneutrophilimmunologytick-borne diseasesIxodes
spellingShingle Pilar Alberdi
Pedro J. Espinosa
Alejandro Cabezas-Cruz
José de la Fuente
Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection
Veterinary Sciences
tick
Anaplasma
apoptosis
neutrophil
immunology
tick-borne diseases
Ixodes
title Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection
title_full Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection
title_fullStr Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection
title_full_unstemmed Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection
title_short Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection
title_sort anaplasma phagocytophilum manipulates host cell apoptosis by different mechanisms to establish infection
topic tick
Anaplasma
apoptosis
neutrophil
immunology
tick-borne diseases
Ixodes
url http://www.mdpi.com/2306-7381/3/3/15
work_keys_str_mv AT pilaralberdi anaplasmaphagocytophilummanipulateshostcellapoptosisbydifferentmechanismstoestablishinfection
AT pedrojespinosa anaplasmaphagocytophilummanipulateshostcellapoptosisbydifferentmechanismstoestablishinfection
AT alejandrocabezascruz anaplasmaphagocytophilummanipulateshostcellapoptosisbydifferentmechanismstoestablishinfection
AT josedelafuente anaplasmaphagocytophilummanipulateshostcellapoptosisbydifferentmechanismstoestablishinfection