Robust Control of a Neurotropic Parasite Through MHC I Presentation by Infected Neurons

Salvioni, Anna; Belloy, Marcy; Lebourg, Aurore; Bassot, Emilie; Cantaloube-Ferrieu, Vincent; Vasseur, Virginie; Blanié, Sophie; Liblau, Roland; Suberbielle, Elsa; Robey, Ellen; Blanchard, Nicolas

doi:10.2139/ssrn.3249820

Cited by 2 publications

(3 citation statements)

References 45 publications

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“…It has been proposed that the presence of this stage in neurons, a cell type known for low MHC-I expression [92], would be sequestered by the immune response. The idea that neurons can act as a refuge has been challenged by evidence that MHC-I presentation of tachyzoite antigens by neurons contributes to parasite control [58]. Imaging of brains from mice chronically infected with T. gondii had higher numbers of Nur77-GFP + OT-I surrounding tachyzoites but as the infection in the brain progresses the decline in levels of TCR engagement correlated with parasite control and the switch from tachyzoite to bradyzoite.…”

Section: Discussionmentioning

confidence: 99%

“…The ability to modify T. gondii to express model antigens such as ovalbumin (OVA), combined with TCR transgenics has provided an important tool to understand T cell responses to this infection [56][57][58][59][60]. This approach allowed the study of early events that lead to parasite specific T cell responses and how these operate in the CNS [18,61,62].…”

Section: Introductionmentioning

confidence: 99%

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Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8⁺T cell response during acute and chronic toxoplasmosis

Shallberg

Phan

Christian

et al. 2022

Preprint

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Initial TCR engagement of CD8+ T cells results in T cell expansion, and these early events influence the generation of diverse effector and memory populations. During infection, some activated T cells re-encounter cognate antigen, but how these events influence local effector responses or formation of memory populations is unclear. To address this issue, OT-I T cells which express the Nur77-GFP reporter of TCR activation were paired with T. gondii that express OVA to assess the impact of TCR activation on CD8+ T cell responses. During acute infection, TCR stimulation in affected tissues correlated with parasite burden and was associated with markers of effector cells while Nur77-GFP- OT-I showed signs of effector memory potential. However, adoptive transfer of Nur77-GFP negative or positive OT-I from infected mice into naive recipients resulted in formation of similar memory populations. During the chronic stage of infection in the CNS, TCR activation was associated with large scale transcriptional changes and the acquisition of an effector T cell phenotype as well as the generation of a population of CD103+ CD69+ Trm like cells. However, while inhibition of parasite replication resulted in reduced effector responses it did not alter the Trm population. These data sets highlight the contribution of recent TCR activation on the phenotypic heterogeneity of the CD8+ T cell response but suggest that this process has a limited impact on memory populations at acute and chronic stages of infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8⁺T cell response during acute and chronic toxoplasmosis

Shallberg

Phan

Christian

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…For all experiments, GFP + type II Prugnaud (Pru) T. gondii, expressing GRA6-OVA under the control of the endogenous GRA6 promoter (Pru.GFP.GRA6-OVA (34) or its derivative Pru.GRA2.GRA6-OVA (36) were used. The GRA2-deficient Pru.GRA2-GRA6-OVA parasites were engineered from the parental Pru.GFP.GRA6-OVA by CRISPR/Cas9-mediated suppression of the GRA2 gene, using phleomycin selection.…”

Section: Toxoplasma Gondii Culture and Infectionmentioning

confidence: 99%

Id2 levels determine the development of effector vs. exhausted tissue-resident memory CD8⁺T cells during CNS chronic infection

Coulibaly,

Nozeran,

Thomann

et al. 2024

Preprint

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Tissue-resident memory T cells (Trm) are essential for regional immunity in non-lymphoid tissues. Although single-cell transcriptomics have revealed Trm heterogeneity in various diseases, the molecular mechanisms behind this diversity are unclear. To investigate this, we used Toxoplasma gondii (T. gondii) infection, which persists in the central nervous system (CNS) and is controlled by brain CD8+ Trm. Our single-cell transcriptomic analysis of brain CD8+ T cells from T. gondii-infected mice showed heterogeneous expression of the transcriptional regulator Id2, correlating with different functional states. Using mixed bone marrow chimeras, we found that Id2-deficiency in T cells caused parasite-specific Trm to develop an altered phenotype with diminished effector functions and reduced expression of CD49a. Furthermore, loss of Id2 in brain-infiltrating CD8+ T cells led to the accumulation of exhausted PD1+Tox+CD8+ Trm cells, while Id2 overexpression repressed T cell exhaustion. Overall, our study shows that Id2 levels dictate the acquisition of effector vs. exhausted phenotypes in CD8+ Trm during chronic CNS infection.

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Robust Control of a Neurotropic Parasite Through MHC I Presentation by Infected Neurons

Cited by 2 publications

References 45 publications

Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8⁺T cell response during acute and chronic toxoplasmosis

Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8⁺T cell response during acute and chronic toxoplasmosis

Id2 levels determine the development of effector vs. exhausted tissue-resident memory CD8⁺T cells during CNS chronic infection

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Robust Control of a Neurotropic Parasite Through MHC I Presentation by Infected Neurons

Cited by 2 publications

References 45 publications

Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+T cell response during acute and chronic toxoplasmosis

Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+T cell response during acute and chronic toxoplasmosis

Id2 levels determine the development of effector vs. exhausted tissue-resident memory CD8+T cells during CNS chronic infection

Contact Info

Product

Resources

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Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8⁺T cell response during acute and chronic toxoplasmosis

Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8⁺T cell response during acute and chronic toxoplasmosis

Id2 levels determine the development of effector vs. exhausted tissue-resident memory CD8⁺T cells during CNS chronic infection