Transcriptomics

Dataset Information

0

Toll-like receptor 2 (TLR2)-TLR9 crosstalk dictates IL-12 family cytokine production in microglia


ABSTRACT: Microglia are the resident mononuclear phagocytes of the CNS parenchyma and represent an initial line of defense against invading microorganisms. Microglia utilize Toll-like receptors (TLRs) for pathogen recognition and TLR2 specifically senses conserved motifs of gram-positive bacteria including lipoproteins, lipoteichoic acids, and peptidoglycan (PGN) leading to cytokine/chemokine production. Interestingly, primary microglia derived from TLR2 knockout (KO) mice over-expressed numerous IL-12 family members, including IL-12p40, IL-12p70, and IL-27 in response to intact S. aureus, but not the less structurally complex TLR2 ligands Pam3CSK4 or PGN. The ability of intact bacteria to augment IL-12 family member expression was specific for gram-positive organisms, since numerous gram-negative strains were unable to elicit exaggerated responses in TLR2 KO microglia. Inhibition of SYK or IRAK4 signaling did not impact heightened IL-12 family member production in S. aureus-treated TLR2 KO microglia, whereas PI3K, MAPK, and JNK inhibitors were all capable of restoring exaggerated cytokine expression to wild type levels. Additionally, elevated IL-12 production in TLR2 KO microglia was ablated by a TLR9 antagonist, suggesting that TLR9 drives IL-12 family member production following exposure to intact bacteria that remains unchecked in the absence of TLR2 signaling. Collectively, these findings indicate crosstalk between TLR2 and TLR9 pathways to regulate IL-12 family member production by microglia. The summation of TLR signals must be tightly controlled to ensure the timely cessation and/or fine tuning of cytokine signaling to avoid nonspecific bystander damage due to sustained IL-12 release.

ORGANISM(S): Mus musculus

PROVIDER: GSE24935 | GEO | 2014/12/22

SECONDARY ACCESSION(S): PRJNA131929

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2014-12-22 | E-GEOD-24935 | biostudies-arrayexpress
| PRJNA131929 | ENA
2008-10-25 | E-GEOD-8960 | biostudies-arrayexpress
2022-01-24 | MODEL2012040002 | BioModels
2016-09-07 | GSE79809 | GEO
2016-09-07 | E-GEOD-79809 | biostudies-arrayexpress
2024-04-11 | GSE263396 | GEO
2011-05-01 | GSE28994 | GEO
2008-09-01 | GSE8960 | GEO
2011-01-27 | E-GEOD-26864 | biostudies-arrayexpress