Differences in the plasma phospholipid profile of patients infected with tick-borne encephalitis virus and co-infected with bacteria

Abstract

Tick-borne encephalitis (TBE) is an infectious viral disease, the pathogenesis of which is still not fully understood. Additionally, TBE can be complicated by co-infections with various bacteria that are also transmitted by ticks, which can affect the proper diagnosis and treatment. Therefore, the aim of the study was to evaluate changes in the plasma phospholipid (PL) and ceramide (CER) profile of patients with TBE and patients with bacterial co-infection (B. burgdorferi or A. phagocytophilum) in relation to healthy subjects. For this purpose, a high-resolution LC-QTOF-MS/MS platform as well as univariate and multivariate statistics were used. The results of this study showed that the levels of phosphatidylcholines (PC) and lysophosphatidylcholines (LPC) species were increased in the plasma of patients with TBE and patients with TBE co-infected with bacteria. On the other hand, observed differences in the content of phosphoethanolamines (PE) and sphingomyelins (SM) make it possible to distinguish TBE patients from patients with co-infections. The opposite direction of changes was also observed in the CER content. This study showed significant modifications to the metabolic pathways of linoleic (LA) and arachidonic acid (AA), as confirmed by the quantitative analysis of these fatty acids. The obtained results allow to distinguish the pathomechanism of TBE from TBE with bacterial co-infection, and consequently may improve the diagnostic process and enable more efficient pharmacotherapy against both pathogens.

Lipid signatures of West Nile virus infection unveil alterations of sphingolipid metabolism providing novel biomarkers

“…However, Cers and dhCers were reduced in infected mice at earlier infection times (7 dpi), suggesting a dynamic interaction of WNV with the sphingolipid pathway. Interestingly, the increase in Cers, which can result cytotoxic, at more advanced infection stages in mice (10 dpi) and in WND patients, is consistent with a role of Cers as drivers of WNV-induced pathology as proposed for other disease models inducers [ 36–39 ], including COVID-19 [ 40 ], Ebola virus fatalities [ 10 ], and in patients infected with tick-borne encephalitis virus (TBEV) [ 41 ]. Circulating Cers play multiple roles in physiology, and their elevation is associated with cancer, autoimmune, metabolic, and neurological diseases, thus making of these lipids potential novel disease biomarkers in diagnostics, determination of disease stage and personalized medicine [ 42 ].…”

“…PE, which was also elevated in mice plasma at middle and late infection stages (7 and 10 dpi) plays multiple functions in health and disease [ 53 ] including neurological disorders [ 54–56 ], and is an important component of viral envelope that contributes to viral entry [ 20 , 57 ]. Moreover, PE and ether derivatives (plasmalogens), were also elevated in patients infected with the flavivirus ZIKV [ 12 ] or TBEV [ 41 ], and elevation of PE has been described in other disorders, such as febrile neutropenia [ 58 ]. As certain PE can exert anti-inflammatory effects [ 59 ], further work to elucidate the role of circulating PE in WNV infection should be conducted.…”

Differences in the phospholipid profile of melanocytes and melanoma cells irradiated with UVA and treated with cannabigerol and cannabidiol

“…We recognized 113 and 104 most abundant phospholipid species in the melanocytes and SK-MEL-5cells, respectively (supplementary Table S1 and Table S2 ). The relative quantification of these phospholipid species was performed based on The peak areas of each phospholipid specie listed in supplementary Tables S3 and Table S4 , were used for relative quantification as previously described 28 .…”

“…Chromatographic separation of phospholipids was performed on the Ascentis Si column (15 cm × 1 mm, 3 μm, Sigma-Aldrich) in gradient elution with the mixture of solvent A [ACN/MeOH/water 50:25:25 (v/v/v) with 1 mM ammonium acetate] and solvent B [ACN/MeOH 60:40 (v/v) with 1 mM ammonium acetate]. The QTOF mass spectrometer operated in negative-ion mode (electrospray voltage, − 3000 V) with capillary temperature, 250 °C and sheath gas flow of 13 L/min, as previously described in details 28 .…”

Changes in cerebrospinal fluid proteome of patients with tick‐borne encephalitis

“…8 This is promoted by cross-activation of the pro-inflammatory and antioxidant transcription factors NF-κB and Nrf2. 9 As a result, oxidative modifications of enzymatic proteins occur, including antioxidant proteins that protect lipids, which promotes lipid peroxidation and their enzymatic metabolism, which leads to significant disturbances in the lipidomic profile, 10 as well as in disturbances at the level of signaling factors. 11 Additionally, there are data on high metalloproteinase 9 (MMP-9) activity in CSF and plasma of TBE patients, [12][13][14] suggesting that the plasma-CSF barrier is disrupted, which may have serious consequences for metabolism and brain function.…”