Immune activation in the central nervous system throughout the course of HIV infection

Spudich, Serena

doi:10.1097/coh.0000000000000243

Cited by 55 publications

(35 citation statements)

References 63 publications

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“…This metabolite has been associated with a tolerizating immune response, especially for T cells (47)(48)(49). It does not seem to be the case for DENV, HIV, and SIV infections since they enhance the immunological status of patients (50)(51)(52)(53)(54). Another common characteristic of these viral infections is the induction of hypergammaglobulinemia (55-59), a hallmark of B cell activity that augments the ASC frequencies (29,60,61).…”

Section: Discussionmentioning

confidence: 99%

Flavivirus-Mediating B Cell Differentiation Into Antibody-Secreting Cells in Humans Is Associated With the Activation of the Tryptophan Metabolism

et al. 2020

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Patients infected with the Dengue virus (DENV) often present with a massive generation of DENV-specific antibody-secreting cells (ASCs) in the blood. In some cases, these ASCs represent more than 50% of the circulating B cells, a higher magnitude than those induced by other infections, vaccinations, and plasma cell lymphomas. However, it remains unclear how the DENV infection elicits this colossal response. To address this issue, we utilised an in vitro strategy to induce human PBMCs of healthy individuals incubated with DENV particles (DENV4 TVP/360) to differentiate into ASCs. As controls, PBMCs were incubated with a mitogen cocktail or supernatants of uninfected C6/36 cells (mock). The ASC phenotype and function were increasingly detected in the DENV and mitogen-cultured PBMCs as compared to mock-treated cells. In contrast to the in vivo condition, secreted IgG derived from the PBMC-DENV culture was not DENV-specific. Lower ASC numbers were observed when inactivated viral particles or purified B cells were added to the cultures. The physical contact was essential between B cells and the remaining PBMCs for the DENV-mediated ASC response. Considering the evidence for the activation of the tryptophan metabolism detected in the serum of Dengue patients, we assessed its relevance in the DENV-mediated ASC differentiation. For this, tryptophan and its respective metabolites were quantified in the supernatants of cell cultures through mass spectrophotometry. Tryptophan depletion and kynurenine accumulation were found in the supernatants of PBMC-DENV cultures, which presented enhanced detection of indoleamine 2,3-dioxygenase 1 and 2 transcripts as compared to controls. In PBMC-DENV cultures, tryptophan and kynurenine levels strongly correlated to the respective ASC numbers, while the kynurenine levels were directly proportional to the secreted IgG titers. Contrastingly, PBMCs incubated with Zika or attenuated Bonezi et al. Dengue-Mediated Antibody-Secreting Cell DifferentiationYellow Fever viruses showed no correlation between their kynurenine concentrations and ASC numbers. Therefore, our data revealed the existence of distinct pathways for the DENV-mediated ASC differentiation and suggest the involvement of the tryptophan metabolism in this cellular process triggered by flavivirus infections.

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Section: Discussionmentioning

confidence: 99%

Flavivirus-Mediating B Cell Differentiation Into Antibody-Secreting Cells in Humans Is Associated With the Activation of the Tryptophan Metabolism

et al. 2020

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“…[25,26] Systemic inflammation responds to cART, but not with resolution to normal, and ongoing macrophage/monocytic associated inflammation is characteristically resistant. [27] Since it is believed that CNS disease is likely driven by monocytic infection, markers of activation of these cells are promising targets for research, with some evidence associating plasma and CSF sCD163 to neuronal damage or impairment.…”

Section: Biomarkers and Handmentioning

confidence: 99%

HIV-associated neurocognitive disorder

Clifford

2017

Current Opinion in Infectious Diseases

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Purpose of review HIV associated neurocognitive disease (HAND) is the most active topic for neuroAIDS investigations at present. Although impairment is mild in patients successfully treated with modern antiviral regimens, it remains an ongoing problem for HIV patients. It is important to update the emerging research concerning HAND. Recent findings The virus enters the brain during acute infection, with evidence for abnormal functioning that may occur early and often persists. Direct relationships with ongoing viral infection continue to be monitored, but chronic inflammation, often associated with monocytes and macrophages appear to be the most likely driver of cognitive dysfunction. Appreciation for cerebrovascular disease as a significant co-morbidity that is associated with cognitive deficits is increasing. Neuroimaging is actively being developed to address detection and measurement of changes in the brain. Optimal cART therapy has vastly improved neurologic outcomes, but so far has not been demonstrated to reverse the remaining mild impairment. Inflammatory and vascular mechanisms of cerebral dysfunction may need to be addressed to achieve better outcomes. Summary Ongoing research is required to improve neurological outcomes for persons living with HIV. It is likely that interventions beyond antiviral approaches will be required to control or reverse HAND.

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“…Sex differences in innate immune sensing and IFN responses by pDCs can also have a critical role in determining differences in HIV-1 disease manifestations between women and men during acute and chronic infection, and require further studying [15]. Cardiovascular disease [16] and neurocognitive disease [17] represent important morbidities in treated patients with HIV-1 infection and have been linked to both adaptive and innate immune activation. Finally, immune activation and inflammation appear to be important contributors to maintenance of HIV viral reservoirs [18], the biggest obstacle to viral eradication and cure.…”

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confidence: 99%