RT Journal Article
T1 Microglial activation by microbial neuraminidase through TLR2 and TLR4 receptors.
A1 Fernández-Arjona, María del Mar
A1 Mateos-Grondona, Jesús
A1 Fernández-Llebrez, Pedro
A1 López-Ávalos, María  Dolores
K1 Sistema nervioso - Inflamación
K1 Agentes antivíricos
K1 Inflamación (Patología) - Aspectos inmunológicos
K1 Virulencia (Microbiología)
K1 Receptores celulares
AB Background: Neuraminidase (NA) is a sialidase present, among various locations, in the envelope/membrane of some bacteria/viruses (e.g., influenza virus), and is involved in infectiveness and/or dispersion. The administration 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. Methods: Mouse strains deficient in either TLR2 (TLR2-/-) or TLR4 (TLR4-/-) were used. NA was injected in the lateral ventricle, and the inflammatory reaction was studied by immunohistochemistry (IBA1 and IL-1β) and qPCR (cytokine response). Also, microglia was isolated from those strains and in vitro stimulated with NA, or with TLR2/TLR4 agonists as positive controls (P3C and LPS respectively). The relevance of the sialidase activity of NA was investigated by stimulating microglia with heat-inactivated NA, or with native NA in the presence of sialidase inhibitors.Results: 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 were only slightly diminished in TLR2-/- mice. Similarly, the NA-induced expression of IL-1β, TNFα, and IL-6 was completely blocked in TLR4-/- mice, and only partially reduced in TLR2-/- mice. In isolated cultured microglia, 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 microglial response.Conclusions: NA is able to directly activate microglial cells, and it does so mostly acting through the TLR4 receptor, while TLR2 has a secondary role. Accordingly, the inflammatory reaction induced by NA in vivo is partially dependent on TLR2, while TLR4 plays a crucial role. Also, the sialidase activity of NA is critical for microglial activation.
PB Springer Nature
YR 2019
FD 2019-12-02
LK https://hdl.handle.net/10630/35269
UL https://hdl.handle.net/10630/35269
LA eng
NO Fernández-Arjona, M.d., Grondona, J.M., Fernández-Llebrez, P. et al. Microglial activation by microbial neuraminidase through TLR2 and TLR4 receptors. J Neuroinflammation 16, 245 (2019). https://doi.org/10.1186/s12974-019-1643-9
NO This work was carried out with funding from Junta de Andalucía, Consejeríade Innovación Ciencia y Empleo (reference P11-CVI-07637) and Ministerio deEconomía, Industria y Competitividad (MINECO, reference SAF2017-83645).These results are part of the Ph.D. Thesis of MFA, who undertook the Ph.D.Program in Advanced Biotechnology, at the University of Málaga.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026