IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.

Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also...

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Autores principales:	Catherine Q Nie, Nicholas J Bernard, M Ursula Norman, Fiona H Amante, Rachel J Lundie, Brendan S Crabb, William R Heath, Christian R Engwerda, Michael J Hickey, Louis Schofield, Diana S Hansen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2e622cd804274a089953399cf44f4366
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spelling	oai:doaj.org-article:2e622cd804274a089953399cf44f43662021-11-25T05:47:08ZIP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.1553-73661553-737410.1371/journal.ppat.1000369https://doaj.org/article/2e622cd804274a089953399cf44f43662009-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19343215/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. In both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific disease appears to be associated with sequestration of parasitized erythrocytes in vascular beds and subsequent recruitment of inflammatory leukocytes. Using a rodent model of cerebral malaria, we have previously found that the majority of T lymphocytes in intravascular infiltrates of cerebral malaria-affected mice express the chemokine receptor CXCR3. Here we investigated the effect of IP-10 blockade in the development of experimental cerebral malaria and the induction of splenic anti-parasite immunity. We found that specific neutralization of IP-10 over the course of infection and genetic deletion of this chemokine in knockout mice reduces cerebral intravascular inflammation and is sufficient to protect P. berghei ANKA-infected mice from fatality. Furthermore, our results demonstrate that lack of IP-10 during infection significantly reduces peripheral parasitemia. The increased resistance to infection observed in the absence of IP-10-mediated cell trafficking was associated with retention and subsequent expansion of parasite-specific T cells in spleens of infected animals, which appears to be advantageous for the control of parasite burden. Thus, our results demonstrate that modulating homing of cellular immune responses to malaria is critical for reaching a balance between protective immunity and immunopathogenesis.Catherine Q NieNicholas J BernardM Ursula NormanFiona H AmanteRachel J LundieBrendan S CrabbWilliam R HeathChristian R EngwerdaMichael J HickeyLouis SchofieldDiana S HansenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 4, p e1000369 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Catherine Q Nie Nicholas J Bernard M Ursula Norman Fiona H Amante Rachel J Lundie Brendan S Crabb William R Heath Christian R Engwerda Michael J Hickey Louis Schofield Diana S Hansen IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.
description	Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. In both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific disease appears to be associated with sequestration of parasitized erythrocytes in vascular beds and subsequent recruitment of inflammatory leukocytes. Using a rodent model of cerebral malaria, we have previously found that the majority of T lymphocytes in intravascular infiltrates of cerebral malaria-affected mice express the chemokine receptor CXCR3. Here we investigated the effect of IP-10 blockade in the development of experimental cerebral malaria and the induction of splenic anti-parasite immunity. We found that specific neutralization of IP-10 over the course of infection and genetic deletion of this chemokine in knockout mice reduces cerebral intravascular inflammation and is sufficient to protect P. berghei ANKA-infected mice from fatality. Furthermore, our results demonstrate that lack of IP-10 during infection significantly reduces peripheral parasitemia. The increased resistance to infection observed in the absence of IP-10-mediated cell trafficking was associated with retention and subsequent expansion of parasite-specific T cells in spleens of infected animals, which appears to be advantageous for the control of parasite burden. Thus, our results demonstrate that modulating homing of cellular immune responses to malaria is critical for reaching a balance between protective immunity and immunopathogenesis.
format	article
author	Catherine Q Nie Nicholas J Bernard M Ursula Norman Fiona H Amante Rachel J Lundie Brendan S Crabb William R Heath Christian R Engwerda Michael J Hickey Louis Schofield Diana S Hansen
author_facet	Catherine Q Nie Nicholas J Bernard M Ursula Norman Fiona H Amante Rachel J Lundie Brendan S Crabb William R Heath Christian R Engwerda Michael J Hickey Louis Schofield Diana S Hansen
author_sort	Catherine Q Nie
title	IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.
title_short	IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.
title_full	IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.
title_fullStr	IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.
title_full_unstemmed	IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.
title_sort	ip-10-mediated t cell homing promotes cerebral inflammation over splenic immunity to malaria infection.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/2e622cd804274a089953399cf44f4366
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IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.

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