Immune Responses to Viruses in the CNS

Schultz, Kimberly L. W.; Griffin, Diane E.

doi:10.1016/b978-0-12-374279-7.14022-6

Cited by 1 publication

(3 citation statements)

References 155 publications

(201 reference statements)

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“…Acute disease consists of weight loss, hunched posture, and paralysis, with severity depending on both host genetics and the strain of SINV ( 10 – 14 ). Recovery from SINV infection of the central nervous system (CNS) involves resident neural cells and infiltrating leukocytes from the periphery ( 15 ). Due to the non-renewable nature of neurons, a successful immune response to viral infection of the CNS cannot depend on cytolytic mechanisms for control and is therefore specialized.…”

Section: Introductionmentioning

confidence: 99%

“…Due to the non-renewable nature of neurons, a successful immune response to viral infection of the CNS cannot depend on cytolytic mechanisms for control and is therefore specialized. Clearance of infectious virus and viral RNA from the CNS is accomplished by the adaptive immune response and involves recruitment of SINV-specific IFNγ-producing T cells and antibody-secreting cells ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…The CNS at steady state is generally void of immunologic activity and has low expression of major histocompatibility complex molecules, and the brain parenchyma contains no conventional lymphatic vessels or professional antigen-presenting cells ( 15 ). Therefore, the activation of lymphocytes in the periphery and their subsequent expansion, release from the CLNs, and trafficking into the CNS implies perturbations to PBMC composition associated with viral encephalitis.…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic and transcriptional changes in peripheral blood mononuclear cells during alphavirus encephalitis in mice

Nguyen,

Bartlett,

Troisi

et al. 2024

mBio

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Sindbis virus (SINV) infection of mice provides a model system for studying the pathogenesis of alphaviruses that infect the central nervous system (CNS) to cause encephalomyelitis. While studies of human viral infections typically focus on accessible cells from the blood, this compartment is rarely evaluated in mice. To bridge this gap, single-cell RNA sequencing (scRNAseq) was combined with flow cytometry to characterize the transcriptional and phenotypic changes of peripheral blood mononuclear cells (PBMCs) from SINV-infected mice. Twenty-one clusters were identified by scRNAseq at 7 days after infection, with a unique cluster and overall increase in naive B cells for infected mice. Uninfected mice had fewer immature T cells and CCR9 + CD4 T cells and a unique immature T cell cluster. Gene expression was most altered in the Ki67 + CD8 T cell cluster, with chemotaxis and proliferation-related genes upregulated. Global analysis indicated metabolic changes in myeloid cells and increased expression of Ccl5 by NK cells. Phenotypes of PBMCs and cells infiltrating the CNS were analyzed by flow cytometry over 14 days after infection. In PBMCs, CD8 and Th1 CD4 T cells increased in representation, while B cells showed a transient decrease at day 5 in total, Ly6a + , and naive cells, and an increase in activated B cells. In the brain, CD8 T cells increased for the first 7 days, while Th1 CD4 T cells and naive and Ly6a + B cells continued to accumulate for 14 days. Therefore, dynamic immune cell changes can be identified in the blood as well as the CNS during viral encephalomyelitis. IMPORTANCE The outcome of viral encephalomyelitis is dependent on the host immune response, with clearance and resolution of infection mediated by the adaptive immune response. These processes are frequently studied in mouse models of infection, where infected tissues are examined to understand the mechanisms of clearance and recovery. However, studies of human infection typically focus on the analysis of cells from the blood, a compartment rarely examined in mice, rather than inaccessible tissue. To close this gap, we used single-cell RNA sequencing and flow cytometry to profile the transcriptomic and phenotypic changes of peripheral blood mononuclear cells (PBMCs) before and after central nervous system (CNS) infection in mice. Changes to T and B cell gene expression and cell composition occurred in PBMC and during entry into the CNS, with CCL5 being a differentially expressed chemokine. Therefore, dynamic changes occur in the blood as well as the CNS during the response of mice to virus infection, which will inform the analysis of human studies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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