HIV Tat-Mediated Induction of Monocyte Transmigration Across the Blood–Brain Barrier: Role of Chemokine Receptor CXCR3

Niu, Fang; Liao, Ke; Hu, Guoku; Moidunny, Shamsudheen; Roy, Sabita; Buch, Shilpa

doi:10.3389/fcell.2021.724970

Cited by 10 publications

(7 citation statements)

References 87 publications

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“…CD204 is a reliable marker of microglia-like cells from the CSF. Microglia and CNS monocytes have been suggested to play a prominent role in HIV neuropathogenesis (11,(25)(26)(27). However, myeloid cells in the CSF are challenging to analyze since their scarcity makes it difficult to characterize cell subsets through traditional flow cytometry-based methods.…”

Section: Resultsmentioning

confidence: 99%

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART

Farhadian¹,

Lindenbaum²,

Zhao³

et al. 2022

JCI Insight

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People with HIV (PWH) on antiretroviral therapy (ART) experience elevated rates of neurological impairment, despite controlling for demographic factors and comorbidities, suggesting viral or neuroimmune etiologies for these deficits. Here, we apply multimodal and cross-compartmental single-cell analyses of paired cerebrospinal fluid (CSF) and peripheral blood in PWH and uninfected controls. We demonstrate that a subset of central memory CD4 + T cells in the CSF produced HIV-1 RNA, despite apparent systemic viral suppression, and that HIV-1–infected cells were more frequently found in the CSF than in the blood. Using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we show that the cell surface marker CD204 is a reliable marker for rare microglia-like cells in the CSF, which have been implicated in HIV neuropathogenesis, but which we did not find to contain HIV transcripts. Through a feature selection method for supervised deep learning of single-cell transcriptomes, we find that abnormal CD8 + T cell activation, rather than CD4 + T cell abnormalities, predominated in the CSF of PWH compared with controls. Overall, these findings suggest ongoing CNS viral persistence and compartmentalized CNS neuroimmune effects of HIV infection during ART and demonstrate the power of single-cell studies of CSF to better understand the CNS reservoir during HIV infection.

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Section: Resultsmentioning

confidence: 99%

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART

Farhadian¹,

Lindenbaum²,

Zhao³

et al. 2022

JCI Insight

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“…For example, in HIV-positive patients, CXCR3-positive astrocytes are found around cerebral infarction, and the number of these cells decreases with the distance from the infarcted tissue [42]. A similar phenomenon can be seen in patients with ischemic stroke, in which the accumulation of CXCR3-positive astrocytes can be seen around the infarction.…”

Section: Nervous System Diseasementioning

confidence: 65%

“…In diseased diseases, microglia-mediated neuronal and glial cell damage is mainly caused by proinflammatory cytokines, which ultimately leads to immune cells participating in the transendothelial migration of blood-brain barrier and subsequent neuronal damage [41]. For example, in HIV-positive patients, CXCR3-positive astrocytes are found around cerebral infarction, and the number of these cells decreases with the distance from the infarcted tissue [42]. A similar phenomenon can be seen in patients with ischemic stroke, in which the accumulation of CXCR3-positive astrocytes can be seen around the infarction.…”

Section: Aberrant Expression Of Cxcr3 In Multiple Diseasesmentioning

confidence: 99%

Research progress of CXCR3 inhibitors

Yuan

2023

Anti-Cancer Drugs

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The human CXCR3 receptor was initially identified and cloned in the mid-1990s. In the process of understanding CXCR3, it gradually found that it plays an important role in the process of a variety of diseases, including inflammation, immune diseases, cancer, cardiovascular diseases, central nervous system diseases, etc., which attracted the attention of many researchers. Subsequently, some small molecule inhibitors targeting CXCR3 receptors were also developed. Unfortunately, no CXCR3 inhibitors have been approved for marketing by FDA. Up to now, only one CXCR3 small molecule inhibitor has entered the clinical trial stage, but it has not achieved ideal results in the end. Therefore, there is still much to think about and explore for the development of CXCR3 inhibitors. This article reviews the important role of CXCR3 in various physiological and pathological processes and some small molecule inhibitors of CXCR3.

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“…Within the myeloid lineage, an increase in CSF1R expression is associated with myeloid cell differentiation and chemotaxis towards tissue-derived ligands 57 , 59 . Contrarily, CXCR3 is highly expressed in peripheral monocytes and is involved in monocyte transmigration into the CNS, where enhanced receptor-ligand binding leads to internalization of the receptor 60 – 64 . In line with these findings, we observed that OPC and SP media resulted in changes in gene expression consistent with a CNS-mimicking microenvironment in contrast to MM.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a high-content compatible platform to assess effects of monocyte-derived factors on neural stem cell proliferation and differentiation

Campo Garcia,

Bueno,

Salla

et al. 2024

Sci Rep

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During neuroinflammation, monocytes that infiltrate the central nervous system (CNS) may contribute to regenerative processes depending on their activation status. However, the extent and mechanisms of monocyte-induced CNS repair in patients with neuroinflammatory diseases remain largely unknown, partly due to the lack of a fully human assay platform that can recapitulate monocyte-neural stem cell interactions within the CNS microenvironment. We therefore developed a human model system to assess the impact of monocytic factors on neural stem cells, establishing a high-content compatible assay for screening monocyte-induced neural stem cell proliferation and differentiation. The model combined monocytes isolated from healthy donors and human embryonic stem cell derived neural stem cells and integrated both cell-intrinsic and -extrinsic properties. We identified CNS-mimicking culture media options that induced a monocytic phenotype resembling CNS infiltrating monocytes, while allowing adequate monocyte survival. Monocyte-induced proliferation, gliogenic fate and neurogenic fate of neural stem cells were affected by the conditions of monocytic priming and basal neural stem cell culture as extrinsic factors as well as the neural stem cell passage number as an intrinsic neural stem cell property. We developed a high-content compatible human in vitro assay for the integrated analysis of monocyte-derived factors on CNS repair.

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HIV Tat-Mediated Induction of Monocyte Transmigration Across the Blood–Brain Barrier: Role of Chemokine Receptor CXCR3

Cited by 10 publications

References 87 publications

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART

Research progress of CXCR3 inhibitors

Establishment of a high-content compatible platform to assess effects of monocyte-derived factors on neural stem cell proliferation and differentiation

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