Plasma n-6 Fatty Acid Levels Are Associated With CD4 Cell Counts, Hospitalization, and Mortality in HIV-Infected Patients

Kabagambe, Edmond K.; Ezeamama, Amara E.; Guwatudde, David; Campos, Hannia; Fawzi, Wafaie W.

doi:10.1097/qai.0000000000001149

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…This may explain the associations between lipid plasma levels and Gag-specific response that we have shown in this work. The specific role of each lipid subclasses on immune cells is uncertain and may vary according to lipid subtypes, but new evidence is emerging in the scenario of HIV infection [[66], [67], [68]]. Modulation of fatty acid synthesis and oxidation pathways could be used as strategies to prevent inflammatory T-cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection

et al. 2019

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Background Approximately 25% of elite controllers (ECs) lose their virological control by mechanisms that are only partially known. Recently, immunovirological and proteomic factors have been associated to the loss of spontaneous control. Our aim was to perform a metabolomic approach to identify the underlying mechanistic pathways and potential biomarkers associated with this loss of control. Methods Plasma samples from EC who spontaneously lost virological control (Transient Controllers, TC, n = 8), at two and one year before the loss of control, were compared with a control group of EC who persistently maintained virological control during the same follow-up period (Persistent Controllers, PC, n = 8). The determination of metabolites and plasma lipids was performed by GC-qTOF and LC-qTOF using targeted and untargeted approaches. Metabolite levels were associated with the polyfunctionality of HIV-specific CD8 + T-cell response. Findings Our data suggest that, before the loss of control, TCs showed a specific circulating metabolomic profile characterized by aerobic glycolytic metabolism, deregulated mitochondrial function, oxidative stress and increased immunological activation. In addition, CD8 + T-cell polyfunctionality was strongly associated with metabolite levels. Finally, valine was the main differentiating factor between TCs and PCs. Interpretation All these metabolomic differences should be considered not only as potential biomarkers but also as therapeutic targets in HIV infection. Fund This work was supported by grants from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Fondos FEDER; Red de Investigación en Sida, Gilead Fellowship program, Spanish Ministry of Education and Spanish Ministry of Economy and Competitiveness.

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Section: Discussionmentioning

confidence: 99%

Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection

et al. 2019

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“…In particular, these studies have shown lower plasma levels of LA (C18:2n-6) in HIV-infected patients with advanced disease [ 24 ]. Interestingly, a study in HIV-infected patients in Uganda showed that the risk of death or hospitalization decreased significantly with an increase in LA or GLA levels, and low levels of LA and GLA were associated with low CD4+ T cell counts [ 25 ]. LA is an essential FA because humans cannot synthesize it.…”

Section: Discussionmentioning

confidence: 99%

“…Most reports have focused on abnormalities in plasma levels of FAs in HIV-infected patients treated with protease inhibitors and in patients with lipodystrophy syndrome [ 20 , 21 , 22 , 23 ]. A few studies, however, have shown alterations in FA composition in untreated HIV-infected children and during early HIV infection, potentially contributing to disease progression in individuals [ 24 , 25 , 26 ]. In support of this notion, there is accumulating evidence that FAs play a crucial role in the innate immune responses against various infections such as influenza and tuberculosis [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Fatty Acids Composition and HIV Infection: Altered Levels of n-6 Polyunsaturated Fatty Acids Are Associated with Disease Progression

Ueland

Waagsbø

Berge

et al. 2023

Viruses

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Fatty acids (FAs) are important regulators of immune responses and innate defense mechanisms. We hypothesized that disturbed FA metabolism could contribute to the progression of HIV infection. Plasma levels of 45 FAs were analyzed with gas chromatography in healthy controls and HIV-infected patients with regard to Mycobacterium avium complex (MAC) infection. In vitro, we assessed MAC-PPD-induced release of inflammatory cytokines in peripheral and bone marrow mononuclear cells (PBMC and BMMC) according to levels of n-6 polyunsaturated fatty acids (PUFAs). While plasma saturated FAs were higher in HIV infection, PUFAs, and in particular the n-6 PUFA arachidonic acid (AA), were lower in patients with advanced disease. The ratio between AA and precursor dihomo-γ-linolenic acid, reflecting Δ5-desaturase activity, was markedly lower and inversely correlated with plasma HIV RNA levels in these patients. Depletion of AA was observed prior to MAC infection, and MAC-PPD-induced release of TNF and IL-6 in PBMC and BMMC was lower in patients with low plasma AA. Our findings suggest that dysregulated metabolism of n-6 PUFAs may play a role in the progression of HIV infection. While high AA may contribute to chronic inflammation in asymptomatic HIV-infected patients, low AA seems to increase the susceptibility to MAC infection in patients with advanced disease.

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“…Dihomo-γ-linolenic acid and arachidonic acid, in particular, are precursors for the synthesis of prostaglandins and eicosanoids, which mediate the effects of type I IFNs during antiviral immune response ( 52 ). It has been previously reported that linoleic acid metabolism positively correlated with CD4 + T cell frequency in HIV-infected patients, whereas its metabolic dysregulation was strongly associated with disease progression and mortality ( 53 ). Finally, RA and bile acid metabolism, known to regulate gut lymphocyte homing and mucosal homeostasis, were significantly boosted in MSC-treated animals.…”

Section: Discussionmentioning

confidence: 99%

Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection

Weber¹,

Walters²,

Kol³

et al. 2021

JCI Insight

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While antiretroviral therapy suppresses HIV replication, it does not eliminate viral reservoirs or restore damaged lymphoid tissue, posing obstacles to HIV eradication. Using the simian immunodeficiency virus (SIV) model of AIDS, we investigated the effect of mesenchymal stem/stromal cell (MSC) infusions on gut mucosal recovery, anti-viral immunity, viral suppression and determined associated molecular/metabolic signatures. MSC administration to SIV-infected macaques resulted in viral reduction and heightened virus-specific responses. Marked clearance of SIV-positive cells from gut mucosal effector sites was correlated with robust regeneration of germinal centers (GC), restoration of follicular B cells, T follicular helper (Tfh) cells, and enhanced antigen presentation by viral trapping within follicular dendritic cell network. Gut transcriptomic analyses showed increased antiviral response mediated by unique pathways of type-I/II IFN signaling, viral restriction factors, innate immunity and B cell proliferation and provided the molecular signature underlying enhanced host immunity. Metabolic analysis revealed strong correlations between B and Tfh cell activation, anti-SIV antibodies, and IL-7 expression with enriched retinol metabolism, which facilitates gut homing of antigen-activated lymphocytes. Our findings discover new MSC functions in modulating anti-viral immunity for enhanced viral clearance predominantly through type-I/II IFN signaling and B cell signature and provide a roadmap for multi-pronged HIV eradication strategies.

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Plasma n-6 Fatty Acid Levels Are Associated With CD4 Cell Counts, Hospitalization, and Mortality in HIV-Infected Patients

Cited by 8 publications

References 29 publications

Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection

Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection

Fatty Acids Composition and HIV Infection: Altered Levels of n-6 Polyunsaturated Fatty Acids Are Associated with Disease Progression

Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection

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