RT Journal Article
T1 Microbial neuraminidase induces TLR4-dependent long-term immune priming in the brain.
A1 Fernández-Arjona, María del Mar
A1 León-Rodríguez, Ana
A1 Mateos-Grondona, Jesús
A1 López-Ávalos, María  Dolores
K1 Neuroglia
K1 Sistema nervioso - Inflamación
K1 Virus de la gripe
K1 Inmunología
AB Innate immune memory explains the plasticity of immune responses after repeated immune stimulation, leading to either enhanced or suppressed immune responses. This process has been extensively reported in peripheralimmune cells and also in the brain. Here we explored two relevant aspects of brain immune priming: its persistence over time and its dependence on TLR receptors. For this purpose, we used an experimental paradigm consisting in applying two inflammatory stimuli three months apart. Wild type, toll-like receptor (TLR) 4 and TLR2 mutant strains were used. The priming stimulus was the intracerebroventricular injection of neuraminidase (an enzyme that is present in various pathogens able to provoke brain infections), which triggers an acute inflammatory process in the brain. The second stimulus was the intraperitoneal injection of lipopolysaccharide (a TLR4 ligand) or Pam3CSK4 (a TLR2 ligand). One day after the second inflammatory challenge the immune response in the brain was examined. In wild type mice, microglial and astroglial density, as well as the expression of 4 out of 5 pro-inflammatory genes studied (TNFa, IL1b, Gal-3, and NLRP3), were increased in mice that received the double stimulus compared to those exposed only to the second one, which were initially injected with saline instead of neuraminidase. Such enhanced response suggests immune training in the brain, which lasts at least 3 months. On the other hand, TLR2 mutants under the same experimental design displayed an enhanced immune response quite similar to that of wild type mice. However, in TLR4 mutant mice the response after the second immune challenge was largely dampened, indicatingthe pivotal role of this receptor in the establishment of immune priming. Our results demonstrate that neuraminidase-induced inflammation primes an enhanced immune response in the brain to a subsequent immune challenge, immune training that endures and that is largely dependent on TLR4 receptor.
PB Frontiers Media
YR 2022
FD 2022-07-28
LK https://hdl.handle.net/10630/35438
UL https://hdl.handle.net/10630/35438
LA eng
NO Fernández-Arjona MdM, León-Rodríguez A, Grondona JM and López-Ávalos MD (2022) Microbial neuraminidase induces TLR4-dependent long-term immune priming in the brain. Front. Cell. Neurosci. 16:945229. doi: 10.3389/fncel.2022.945229
NO This work was supported by funding from Ministerio de Economía, Industria y Competitividad (Spanish Government; grant number SAF2017-83645). AL-R received fellowships from Plan Propio de Investigación y Transferencia (Universidad de Málaga, Spain). The Olympus VS120 microscope was acquired with FEDER funds from the European Union.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026