The Absence of CXCL10 Activity Does Not Affect the Capability of CD8<sup>+</sup> T Cells to Migrate and Eliminate the Tissue Cysts of <i>Toxoplasma gondii</i> from the Brains of Chronically Infected Mice
<i>Toxoplasma gondii</i> forms tissue cysts in neurons and astrocytes in the brain to establish chronic infection, and astrocytes express the CXCL10 chemokine in chronically infected mice. Since chemokines mediate the migration of T cells to attack their targets, and since CXCL10 plays k...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
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| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/12/11/2172 |
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| Summary: | <i>Toxoplasma gondii</i> forms tissue cysts in neurons and astrocytes in the brain to establish chronic infection, and astrocytes express the CXCL10 chemokine in chronically infected mice. Since chemokines mediate the migration of T cells to attack their targets, and since CXCL10 plays key roles in T cell-mediated control of the proliferation of tachyzoites (the acute stage form) of <i>T. gondii</i> during the acute stage of infection, we examined whether CXCL10 is involved in recruiting anti-cyst CD8<sup>+</sup> cytotoxic T cells to eliminate the cysts in their brains. We employed adoptive transfer of CD8<sup>+</sup> immune T cells to infected, T cell-deficient SCID and RAG1<sup>−/−</sup> mice in combination with blocking CXCL10 activity by neutralizing antibody or a deletion of this chemokine gene. The treatment of chronically infected (infected and treated with sulfadiazine) SCID mice with the anti-CXCL10 antibody did not inhibit the recruitment of the transferred CD8<sup>+</sup> T cells into their brains and the removal of cerebral <i>T. gondii</i> cysts by the T cells. In addition, the neutralization of CXCL10 did not reduce the cerebral expression of mRNA for the mediators (perforin and granzyme B [GzmB]) of the cytotoxic activity of CD8<sup>+</sup> T cells in the SCID mice. Consistently, the adoptive transfer of CD8<sup>+</sup> immune T cells to chronically infected RAG1<sup>−/−</sup>CXCL10<sup>−/−</sup> mice did not show any defects in recruiting the CD8<sup>+</sup> T cells into their brains and eliminating the cysts when compared to infected RAG1<sup>−/−</sup> mice. The former rather displayed enhanced cyst removal with increased cerebral expression of GzmB mRNA. These results indicate that the absence of CXCL10 activity does not ablate the capability of CD8<sup>+</sup> cytotoxic T cells to migrate into the brain and eliminate <i>T. gondii</i> cysts from the brains of chronically infected mice. These results also suggest that the immune system utilizes distinct chemokines to control <i>T. gondii</i> depending on the two different life cycle stages, tachyzoite and cyst, of this protozoan parasite. |
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| ISSN: | 2076-2607 |