RT Conference Proceedings
T1 Neuraminidase-induced neuroinflammation is largely dependent on microglial TLR4 receptor
A1 Fernández-Arjona, María del Mar
A1 Mateos-Grondona, Jesús
A1 Fernández-Llebrez, Pedro
A1 López-Ávalos, María  Dolores
K1 Enzimas víricas
K1 Enzimas microbianas
K1 Sistema nervioso - Inflamación
K1 Experimentación animal
AB The sialidase neuraminidase (NA) cleaves terminal sialic acid from glycoproteins and glycolipids. Among its various locations, it is present in the envelope/membrane of some bacteria/viruses (e.g. influenza virus), where it is involved in infectiveness and dispersion. The injection of NA within the brain lateral ventricle represents a model of acute sterileinflammation. The relevance of the toll-like receptors TLR2 and TLR4 (particularly those inmicroglial cells) in such process was investigated using mouse strains deficient in thesereceptors. In septofimbria and hypothalamus, IBA1-positive and IL-1β-positive cell countsincreased after NA injection in wild type (WT) mice. In TLR4-/- mice such increases were largely abolished, while only slightly affected in TLR2-/- mice. Similarly, the NA-inducedexpression of IL-1β, TNFα and IL-6 (evaluated by qPCR) was completely blocked in TLR4-/-mice, and only partially reduced in TLR2-/- mice. Microglia was isolated from the three mousestrains and exposed to NA or to specific TLR2 and TLR4 agonists (Pam3CSK4 and LPSrespectively) in vitro. NA induced a cytokine response (IL-1β, TNFα and IL-6) in WTmicroglia, but was unable to do so in TLR4-/- microglia; TLR2 deficiency partially affectedthe NA-induced microglia response. To investigate if such response of microglial cells to NAwas dependent on the sialidase activity of the enzyme, WT microglia was exposed in vitro toNA previously inactivated with heat, or inhibited with two different sialidase inhibitors(oseltamivir phosphate and N-acetyl-2,3-dehydro-2-deoxyneuraminic acid). In all cases, NA-induced microglia activation was dependent on the intact sialidase activity of NA. Therefore,we conclude that NA is able to directly activate microglial cells, mostly through TLR4receptor and due to its sialidase activity. Accordingly, the inflammatory reaction induced byNA in vivo is partially dependent on TLR2, while TLR4 plays a crucial role.
YR 2019
FD 2019-10-01
LK https://hdl.handle.net/10630/18498
UL https://hdl.handle.net/10630/18498
LA eng
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026