2026-05-30T02:12:28Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/184982026-02-03T11:46:41Zcom_10630_2254col_10630_37959

Neuraminidase-induced neuroinflammation is largely dependent on microglial TLR4 receptor Fernández-Arjona, María del Mar Mateos-Grondona, Jesús Fernández-Llebrez, Pedro López-Ávalos, María Dolores Enzimas víricas Enzimas microbianas Sistema nervioso - Inflamación Experimentación animal 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 sterile inflammation. The relevance of the toll-like receptors TLR2 and TLR4 (particularly those in microglial cells) in such process was investigated using mouse strains deficient in these receptors. In septofimbria and hypothalamus, IBA1-positive and IL-1β-positive cell counts increased 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-induced expression 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 mouse strains and exposed to NA or to specific TLR2 and TLR4 agonists (Pam3CSK4 and LPS respectively) in vitro. NA induced a cytokine response (IL-1β, TNFα and IL-6) in WT microglia, but was unable to do so in TLR4-/- microglia; TLR2 deficiency partially affected the NA-induced microglia response. To investigate if such response of microglial cells to NA was dependent on the sialidase activity of the enzyme, WT microglia was exposed in vitro to NA 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 TLR4 receptor and due to its sialidase activity. Accordingly, the inflammatory reaction induced by NA in vivo is partially dependent on TLR2, while TLR4 plays a crucial role. 2019-10-01T06:51:28Z 2019-10-01T06:51:28Z 2019 2019-10-01 conference output https://hdl.handle.net/10630/18498 eng 18th National Meeting of the Spanish Society of Neuroscience Santiago de Compostela (Spain) 4-6 septiembre 2019 open access