Blood-CSF barrier and compartmentalization of CNS cellular immune response in HIV infection

Almeida, Sérgio Monteiro de; Rotta, Indianara; Ribeiro, Cléa Elisa Lopes; Smith, Davey M.; Wang, Ruiyi; Judicello, Jennifer; Potter, Michael; Vaida, Florin; Letendre, Scott; Ellis, Ronald J.

doi:10.1016/j.jneuroim.2016.10.009

Cited by 27 publications

(20 citation statements)

References 41 publications

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“…(8) The cellular immune response to HIV in the CSF was different from that in serum. It was stronger in the CNS than in the peripheral blood, indicating that the CNS cellular immune response in HIV infection was compartmentalized, in accordance with previously described (de Almeida et al, 2016B). (9) Several biomarkers had levels higher in the CSF than serum, clearly showing intrathecal production.…”

Section: Discussionsupporting

confidence: 90%

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization—case study

et al. 2017

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Despite the effective suppression of viremia with antiretroviral (ARV) therapy, HIV can still replicate in the CNS. This was a longitudinal study of the CSF and serum dynamics of several biomarkers related to inflammation, the blood brain barrier, neuronal injury as well IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization. The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation-sequencing (NGS) and F-statistics analysis (FST), of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples (PBMC). The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction and an increase in neuronal injury biomarkers with demyelization. Conclusions Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

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Section: Discussionsupporting

confidence: 90%

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization—case study

et al. 2017

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“…Moreover, previous studies found similar frequencies of HIVC and B neurological and psychiatric manifestations as well as similar stimulation of ß-chemokines and inflammatory bio-markers in the CSF (de Almeida et al 2013, 2016a, b). These findings are contrary to a previous report that HIV-1 subtype C was less neuropathogenic than subtype B (Satishchandra et al 2000).…”

Section: Discussionsupporting

confidence: 65%

“…(7) The cellular immune response to HIV in the CSF was different from that in the serum. The response was stronger in the CNS than that in the peripheral blood, indicating that the CNS cellular immune response was compartmentalized (de Almeida et al 2016a). (8) The levels of several biomarkers were higher in the CSF than those in the serum, strongly indicating intrathecal production.…”

Section: Discussionmentioning

confidence: 99%

Transient and asymptomatic meningitis in human immunodeficiency virus-1 subtype C: a case study of genetic compartmentalization and biomarker dynamics

et al. 2018

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Human immunodeficiency virus (HIV) genetic compartmentalization is defined as genetic differences in HIV in different tissue compartments or subcompartments that characterize viral quasispecies. This descriptive, longitudinal study assessed the dynamics of inflammation, humoral immune response, blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier, as well as neuronal injury biomarkers in serially obtained CSF and serum samples from an antiretroviral (ARV) therapy-naïve patient with HIV-1 subtype C with CSF HIV genetic compartmentalization that resolved spontaneously without ARV treatment. The first CSF sample showed an increase in white blood cell (WBC) count (382 cells/mm3) and a marked increase in the levels of inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)α, interleukin (IL)-10, IP-10, and regulated on activation, normal T cell expressed and secreted (RANTES), which raise the suspicion of dual infection. Serum sample analysis showed all cytokine levels to be normal, with only IP-10 slightly increased. These results corroborate the hypothesis that the CNS immunologic response in a patient with HIV infection was independent of the systemic immunologic response. The patient also had persistently elevated levels of sCD14, neopterin, and β2M, which were strongly suggestive of persistent CNS immunologic stimulation. This report describes a patient with HIV subtype C who developed a transient episode of asymptomatic HIV meningitis with compartmentalization of HIV in the CSF that resolved independently of ARV therapy. Extensive CSF studies were performed as part of an ongoing longitudinal study, which revealed CNS immune abnormalities. This case presents evidence of HIV-1 subtype C neurotropism and compartmentalization.

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“…Increased protein expression of MRP1 and Pgp at the BBB further limits the brain penetration of antiretrovirals and may contribute to the variability in response to HIV therapies (140). BCSFB integrity, analyzed by the CSF albumin/serum albumin quotient ( Q Alb = Alb CSF /Alb serum ), was reduced in HIV patients but not in uninfected controls; however, there is a lack of information on transporter expression in choroid plexus epithelial cells in HIV infection (143).…”

Section: Changes In Expression/function Of Bbb and Bcsfb Transportersmentioning

confidence: 99%

SLC and ABC Transporters: Expression, Localization, and Species Differences at the Blood-Brain and the Blood-Cerebrospinal Fluid Barriers

Morris

Rodriguez-Cruz

Felmlee

2017

AAPS J

129

107

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The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) separate the brain and cerebrospinal fluid (CSF) from the systemic circulation and represent a barrier to the uptake of both endogenous compounds and xenobiotics into the brain. For compounds whose passive diffusion is limited due to their ionization or hydrophilicity, membrane transporters can facilitate their uptake across the BBB or BCSFB. Members of the solute carrier (SLC) and ATP-binding case (ABC) families are present on these barriers. Differences exist in the localization and expression of transport proteins between the BBB and BCSFB, resulting in functional differences in transport properties. This review focuses on the expression, membrane localization, and different isoforms present at each barrier. Diseases that affect the central nervous system including brain tumors, HIV, Alzheimer's disease, Parkinson's disease, and stroke affect the integrity and expression of transporters at the BBB and BCSFB and will be briefly reviewed.

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Blood-CSF barrier and compartmentalization of CNS cellular immune response in HIV infection

Cited by 27 publications

References 41 publications

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization—case study

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization—case study

Transient and asymptomatic meningitis in human immunodeficiency virus-1 subtype C: a case study of genetic compartmentalization and biomarker dynamics

SLC and ABC Transporters: Expression, Localization, and Species Differences at the Blood-Brain and the Blood-Cerebrospinal Fluid Barriers

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