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CXCL9 is important for recruiting immune T cells into the brain and inducing an accumulation of the T cells to the areas of tachyzoite proliferation to prevent reactivation of chronic cerebral infection with Toxoplasma gondii.

Abstract
T cells are required to maintain the latency of chronic infection with Toxoplasma gondii in the brain. Here, we examined the role of non-glutamic acid-leucine-arginine CXC chemokine CXCL9 for T-cell recruitment to prevent reactivation of infection with T. gondii. Severe combined immunodeficient (SCID) mice were infected and treated with sulfadiazine to establish a chronic infection. Immune T cells from infected wild-type mice were transferred into the SCID mice in combination with treatment with anti-CXCL9 or control sera. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Numbers of CD4(+) and CD8(+) T cells isolated from the brains were markedly less in mice treated with anti-CXCL9 serum than in mice treated with control serum at 3 days after sulfadiazine discontinuation. Amounts of tachyzoite (acute stage form of T. gondii)-specific SAG1 mRNA and numbers of foci associated with tachyzoites were significantly greater in the former than the latter at 5 days after sulfadiazine discontinuation. An accumulation of CD3(+) T cells into the areas of tachyzoite growth was significantly less frequent in the SCID mice treated with anti-CXCL9 serum than in mice treated with control serum. These results indicate that CXCL9 is crucial for recruiting immune T cells into the brain and inducing an accumulation of the T cells into the areas where tachyzoites proliferate to prevent reactivation of chronic T. gondii infection.
AuthorsEri Ochiai, Qila Sa, Morgan Brogli, Tomoya Kudo, Xisheng Wang, Jitender P Dubey, Yasuhiro Suzuki
JournalThe American journal of pathology (Am J Pathol) Vol. 185 Issue 2 Pg. 314-24 (Feb 2015) ISSN: 1525-2191 [Electronic] United States
PMID25432064 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Chemokine CXCL9
  • Cxcl9 protein, mouse
Topics
  • Animals
  • Brain (immunology, parasitology, pathology)
  • CD4-Positive T-Lymphocytes (immunology, pathology)
  • CD8-Positive T-Lymphocytes (immunology, pathology)
  • Cell Movement (genetics, immunology)
  • Cell Proliferation
  • Chemokine CXCL9 (genetics, immunology)
  • Chronic Disease
  • Encephalitis (genetics, immunology, parasitology, pathology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Toxoplasma (immunology)
  • Toxoplasmosis (genetics, immunology, pathology)

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