| First Author | Hoogland ICM | Year | 2022 |
| Journal | Neurosci Lett | Volume | 790 |
| Pages | 136894 | PubMed ID | 36183964 |
| Mgi Jnum | J:329984 | Mgi Id | MGI:7355871 |
| Doi | 10.1016/j.neulet.2022.136894 | Citation | Hoogland ICM, et al. (2022) Microglial response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice after systemic stimulation with Escherichia coli. Neurosci Lett 790:136894 |
| abstractText | BACKGROUND: Systemic infection is an important risk factor for delirium, associated with neurodegeneration and subsequent cognitive impairment in older people. Microglial cell response is a known key player in this process and we hypothesize that the triggering receptor expressed on myeloid cells 2 (TREM2) plays an important role in the regulation of this response. METHODS: 8- to 10-week old male wild-type (WT) and TREM2 knock-out (Trem2(-/-)) mice were intraperitoneally inoculated with live Escherichia coli (E. coli) or saline. After inoculation, all mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h and were sacrificed after 2 and 3 days. Microglial response was determined by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. mRNA expression of pro- and anti-inflammatory mediators was measured to quantify the inflammatory response. RESULTS: We observed increased Iba-1 positive cells number in thalamus of Trem2(-/-) mice at 3d after inoculation compared to WT mice (mean 120 cell/mm(2) [SD 8] vs 105 cell/mm(2) [SD 11]; p = 0.03). Flow cytometry showed no differences in forward scatter or expression of CD11b, CD45 and CD14 between WT and Trem2(-/-) mice. The brain mRNA expression levels of tumor necrosis factor alpha (TNF-alpha) of Trem2(-/-) mice at 2d were higher compared to WT mice (p = 0.003). Higher mRNA expression of interleukin 1 beta (IL-1beta), Iba-1, CD11b and mitogen-activated protein kinase 1 (MAPK-1) was found in brain of WT mice at 2d compared to Trem2(-/-) mice (respectively p = 0.02; p = 0.001; p = 0.03 and p = 0.02). In spleen there were no differences in inflammatory mediators, between WT and Trem2(-/-) mice. INTERPRETATION: Although the loss of function of TREM2 during systemic infection led to an increased number of activated microglia in the thalamus, we did not observe a consistent increase in expression of inflammatory genes in the brain. The role of TREM2 in the neuro-inflammatory response following systemic infection therefore appears to be limited. |
