Engineering Attenuated Virulence of a Theileria annulata–Infected Macrophage

Collection with item attached
2014_11
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/2154.do
DOI
http://dx.doi.org/10.1371/journal.pntd.0003183
journal_title
PLoS Neglected Tropical Diseases
eissn
1935-2735
publisher_name
Public Library of Science
article_id
10.1371/journal.pntd.0003183
article_title
Engineering Attenuated Virulence of a Theileria annulata–Infected Macrophage
surname
Echebli
given_names
Nadia
address
Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France
Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, France
surname
Mhadhbi
given_names
Moez
address
Laboratoire de Parasitologie, Ecole Nationale de Médecine Vétérinaire, Sidi Thabet, Tunisia
surname
Chaussepied
given_names
Marie
address
Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France
Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, France
surname
Vayssettes
given_names
Catherine
address
Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France
Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, France
surname
Di Santo
given_names
James P.
address
Innate Immunity Unit, Department of Immunology, Pasteur Institute, Paris, France
Inserm U688, Pasteur Institute, Paris, France
surname
Darghouth
given_names
Mohamed Aziz
email
damaziz@yahoo.fr
address
Laboratoire de Parasitologie, Ecole Nationale de Médecine Vétérinaire, Sidi Thabet, Tunisia
Institution de la Recherche et de l'Enseignement Supérieur Agricoles, Tunis, Tunisia
surname
Langsley
given_names
Gordon
email
gordon.langsley@inserm.fr
address
Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France
Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, France
pub_date:2014-11-06
history_received:2014-05-26
history_accepted:2014-08-12
volume
8
issue
11
title
Author Summary
p
Tropical theileriosis is a leukaemia-like disease of cattle caused by the Apicomplexa parasite Theileria annulata. Live attenuated vaccines are used to control the mortality and morbidity of tropical theileriosis and each endemic country produces its own vaccine by isolating a virulent clinical isolate and then growing the infected and transformed macrophages for many months in the laboratory. With time, virulence is progressively lost, and loss is evaluated from time to time by injecting infected macrophages into calves and monitoring any resulting pathology. If the calves demonstrate clinical symptoms, in vitro culture of vaccine lines continues, and eventually attenuation is achieved after approximately two years. The process is empirical, and with time in culture the infected macrophage lines lose their vaccine potential such that when cattle are injected the immune response to the vaccine can be compromised. To circumvent these problems we engineered the rapid loss of a host macrophage virulence trait and obtained complete attenuation of dissemination of T. annulata–transformed macrophages when tested in an immune-compromised mouse model. This rational, rather than empirical, approach now allows injecting into calves Theileria-infected macrophages engineered for attenuation to evaluate the role of Theileria-infected macrophage dissemination in the pathology of tropical theileriosis.
copyright
© 2014 Echebli et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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