MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.

The dual specific phosphatase, MAP kinase phosphatase-2 (MKP-2) has recently been demonstrated to negatively regulate macrophage arginase-1 expression, while at the same time to positively regulate iNOS expression. Consequently, MKP-2 is likely to play a significant role in the host interplay with i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stuart Woods, Juliane Schroeder, Helen A McGachy, Robin Plevin, Craig W Roberts, James Alexander
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/24e880428d8349f5a3197c0ce0bbafef
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:24e880428d8349f5a3197c0ce0bbafef
record_format	dspace
spelling	oai:doaj.org-article:24e880428d8349f5a3197c0ce0bbafef2021-11-18T06:07:46ZMAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.1553-73661553-737410.1371/journal.ppat.1003535https://doaj.org/article/24e880428d8349f5a3197c0ce0bbafef2013-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23966857/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The dual specific phosphatase, MAP kinase phosphatase-2 (MKP-2) has recently been demonstrated to negatively regulate macrophage arginase-1 expression, while at the same time to positively regulate iNOS expression. Consequently, MKP-2 is likely to play a significant role in the host interplay with intracellular pathogens. Here we demonstrate that MKP-2(-/-) mice on the C57BL/6 background have enhanced susceptibility compared with wild-type counterparts following infection with type-2 strains of Toxoplasma gondii as measured by increased parasite multiplication during acute infection, increased mortality from day 12 post-infection onwards and increased parasite burdens in the brain, day 30 post-infection. MKP-2(-/-) mice did not, however, demonstrate defective type-1 responses compared with MKP-2(+/+) mice following infection although they did display significantly reduced serum nitrite levels and enhanced tissue arginase-1 expression. Early resistance to T. gondii in MKP-2(+/+), but not MKP-2(-/-), mice was nitric oxide (NO) dependent as infected MKP-2(+/+), but not MKP-2(-/-) mice succumbed within 10 days post-infection with increased parasite burdens following treatment with the iNOS inhibitor L-NAME. Conversely, treatment of infected MKP-2(-/-) but not MKP-2(+/+) mice with nor-NOHA increased parasite burdens indicating a protective role for arginase-1 in MKP-2(-/-) mice. In vitro studies using tachyzoite-infected bone marrow derived macrophages and selective inhibition of arginase-1 and iNOS activities confirmed that both iNOS and arginase-1 contributed to inhibiting parasite replication. However, the effects of arginase-1 were transient and ultimately the role of iNOS was paramount in facilitating long-term inhibition of parasite multiplication within macrophages.Stuart WoodsJuliane SchroederHelen A McGachyRobin PlevinCraig W RobertsJames AlexanderPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 8, p e1003535 (2013)
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 Stuart Woods Juliane Schroeder Helen A McGachy Robin Plevin Craig W Roberts James Alexander MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.
description	The dual specific phosphatase, MAP kinase phosphatase-2 (MKP-2) has recently been demonstrated to negatively regulate macrophage arginase-1 expression, while at the same time to positively regulate iNOS expression. Consequently, MKP-2 is likely to play a significant role in the host interplay with intracellular pathogens. Here we demonstrate that MKP-2(-/-) mice on the C57BL/6 background have enhanced susceptibility compared with wild-type counterparts following infection with type-2 strains of Toxoplasma gondii as measured by increased parasite multiplication during acute infection, increased mortality from day 12 post-infection onwards and increased parasite burdens in the brain, day 30 post-infection. MKP-2(-/-) mice did not, however, demonstrate defective type-1 responses compared with MKP-2(+/+) mice following infection although they did display significantly reduced serum nitrite levels and enhanced tissue arginase-1 expression. Early resistance to T. gondii in MKP-2(+/+), but not MKP-2(-/-), mice was nitric oxide (NO) dependent as infected MKP-2(+/+), but not MKP-2(-/-) mice succumbed within 10 days post-infection with increased parasite burdens following treatment with the iNOS inhibitor L-NAME. Conversely, treatment of infected MKP-2(-/-) but not MKP-2(+/+) mice with nor-NOHA increased parasite burdens indicating a protective role for arginase-1 in MKP-2(-/-) mice. In vitro studies using tachyzoite-infected bone marrow derived macrophages and selective inhibition of arginase-1 and iNOS activities confirmed that both iNOS and arginase-1 contributed to inhibiting parasite replication. However, the effects of arginase-1 were transient and ultimately the role of iNOS was paramount in facilitating long-term inhibition of parasite multiplication within macrophages.
format	article
author	Stuart Woods Juliane Schroeder Helen A McGachy Robin Plevin Craig W Roberts James Alexander
author_facet	Stuart Woods Juliane Schroeder Helen A McGachy Robin Plevin Craig W Roberts James Alexander
author_sort	Stuart Woods
title	MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.
title_short	MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.
title_full	MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.
title_fullStr	MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.
title_full_unstemmed	MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.
title_sort	map kinase phosphatase-2 plays a key role in the control of infection with toxoplasma gondii by modulating inos and arginase-1 activities in mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/24e880428d8349f5a3197c0ce0bbafef
work_keys_str_mv	AT stuartwoods mapkinasephosphatase2playsakeyroleinthecontrolofinfectionwithtoxoplasmagondiibymodulatinginosandarginase1activitiesinmice AT julianeschroeder mapkinasephosphatase2playsakeyroleinthecontrolofinfectionwithtoxoplasmagondiibymodulatinginosandarginase1activitiesinmice AT helenamcgachy mapkinasephosphatase2playsakeyroleinthecontrolofinfectionwithtoxoplasmagondiibymodulatinginosandarginase1activitiesinmice AT robinplevin mapkinasephosphatase2playsakeyroleinthecontrolofinfectionwithtoxoplasmagondiibymodulatinginosandarginase1activitiesinmice AT craigwroberts mapkinasephosphatase2playsakeyroleinthecontrolofinfectionwithtoxoplasmagondiibymodulatinginosandarginase1activitiesinmice AT jamesalexander mapkinasephosphatase2playsakeyroleinthecontrolofinfectionwithtoxoplasmagondiibymodulatinginosandarginase1activitiesinmice
_version_	1718424524071895040

MAP kinase phosphatase-2 plays a key role in the control of infection with Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.

Ejemplares similares