Deficiency of Toll-like receptor 2 is a driver of sex-related compositional and structural rearrangements of membrane lipids

Ica, Raluca Sabina; Mlinac-Jerkovic, Kristina; Stojanović, Mario; Roxana Biricioiu, Maria; Puljko, Borna; Maček-Hrvat, Nikolina; Radmilović, Marina Dobrivojević; Korade, Željka; Mirnics, Karoly; Clemmer, David E.; Zamfir, Alina D.; Kalanj-Bognar, Svjetlana (2025) Deficiency of Toll-like receptor 2 is a driver of sex-related compositional and structural rearrangements of membrane lipids. Communications Chemistry, 8 (1). ISSN 2399-3669

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Abstract

The behavior and function of membrane microdomains is shaped by the intricate liaison between the most complex glycosphingolipids-gangliosides, cholesterol and specific classes of transmembrane proteins. Toll-like receptor 2 (TLR2), a pattern recognition receptor localized in lipid rafts, is implicated in different membrane-associated events, some of which overlap between gangliosides and TLR2, such as pathogen recognition and neuroinflammation. Aiming to determine whether TLR2 deficiency influences on the composition and arrangement of membrane lipids, we examined cortical tissue of TLR2-deficient and control mice by in-depth glycolipidomic profiling along with transcriptomic analysis of genes involved in ganglioside and cholesterol metabolism. A multi-level experimental approach, including powerful high-resolution mass spectrometry techniques, provided a detailed lipidomic data and elaborate structural characterization of brain gangliosidome and sterolome in TLR2 deficiency. The results demonstrate the presence of distinct brain glycolipidomic and sterol pattern as well as lipid redistribution within the membrane fractions in TLR2 deficiency. In addition, the findings speak in favor of a sex-specific structural and functional partnership of TLR2, gangliosides and cholesterol in the brain tissue that may act as a connection point integrating extracellular stimuli and modulating neuroimmune response in a sex-dependent manner.

Item Type:	Article
Uncontrolled Keywords:	Lipidomics; mass spectrometry; neurochemistry; Toll-like receptor 2
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Neuroscience
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Molekularni biljezi vulnerabilnosti, adaptacije i plastičnosti neurona u akutnoj i kroničnoj ozljedi mozga-NeuroReact Svjetlana Kalanj-Bognar IP-2016-06-8636 HRZZ Istraživanje i dijagnostika malignih, infektivnih i rijetkih metaboličkih bolesti temeljena na MALDI TOF tehnologiji- Željko Debeljak KK.01.1.1.02.0015 EK
Depositing User:	Ana Zečević
Date Deposited:	20 May 2026 07:22
URI:	https://fulir.irb.hr:/id/eprint/11972
DOI:	10.1038/s42004-025-01766-x

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