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BACKGROUND: Multiple host factors may influence immune reconstitution in HIV-infected people after the initiation of suppressive antiretroviral therapy (ART). Aberrant metabolic pathways have been reported in people with HIV (PWH) on ART. We hypothesized that alterations in plasma metabolites were associated with immune recovery following ART. METHODS: In this cross-sectional study, the plasma metabolomic profiles of PWH on ART were evaluated. PWH of slow and fast immune recovery were classified by increase in CD4 T cells following 2 years of ART. Targeted plasma metabolite profiling by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to determine metabolite signatures for HIV recovery identified >200 metabolites. RESULTS: Notably, indole-3-propionic acid was downregulated during HIV, possibly reflecting impaired gastrointestinal epithelium homeostasis. The most important metabolite discriminating between the PWH with fast and slow immune recovery was cysteine. Upregulated cysteine and cysteine pathways may contribute to redox-balance maintenance and T-cell function in PWH with fast immune recovery. Additionally, serine and glycine metabolism and bile acid biosynthesis were the most perturbed metabolic pathways in PWH. CONCLUSIONS: These results provide a starting point for developing biomarker candidates for immune recovery in PWH on ART and provide insight into the interplay of metabolism and immune response in HIV infection.

Contains fulltext : 194630.pdf (publisher's version ) (Open Access), One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-beta (Abeta) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Abeta in the brain. In addition to influencing Abeta metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1deltaE9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Abeta morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.

Contains fulltext : 194630.pdf (publisher's version ) (Open Access), One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-beta (Abeta) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Abeta in the brain. In addition to influencing Abeta metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1deltaE9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Abeta morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.

Contains fulltext : 194630.pdf (publisher's version ) (Open Access), One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-beta (Abeta) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Abeta in the brain. In addition to influencing Abeta metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1deltaE9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Abeta morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.