Research output: Contribution to journal › Article › Academic › peer-review
Microglial response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice after systemic stimulation with Escherichia coli. / Hoogland, Inge C. M.; Yik, Jutka; Westhoff, Dunja et al.
In: Neuroscience letters, Vol. 790, 136894, 01.11.2022, p. 136894.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Microglial response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice after systemic stimulation with Escherichia coli
AU - Hoogland, Inge C. M.
AU - Yik, Jutka
AU - Westhoff, Dunja
AU - Engelen-Lee, Joo-Yeon
AU - Valls Seron, Merche
AU - Man, Wing-Kit
AU - Houben-Weerts, Judith H. P. M.
AU - Tanck, Michael W.
AU - van Westerloo, David J.
AU - van der Poll, Tom
AU - van Gool, Willem A.
AU - van de Beek, Diederik
N1 - Publisher Copyright: © 2022 The Author(s)
PY - 2022/11/1
Y1 - 2022/11/1
N2 - 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/mm2 [SD 8] vs 105 cell/mm2 [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-α) of Trem2-/- mice at 2d were higher compared to WT mice (p = 0.003). Higher mRNA expression of interleukin 1 beta (IL-1β), 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.
AB - 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/mm2 [SD 8] vs 105 cell/mm2 [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-α) of Trem2-/- mice at 2d were higher compared to WT mice (p = 0.003). Higher mRNA expression of interleukin 1 beta (IL-1β), 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.
KW - Escherichia coli
KW - Knock-out
KW - Microglia
KW - Microglial activation
KW - Mouse model
KW - Neuro-inflammation
KW - Systemic infection
KW - TREM2
KW - Triggering receptor expressed on myeloid cells 2
UR - http://www.scopus.com/inward/record.url?scp=85139049193&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2022.136894
DO - 10.1016/j.neulet.2022.136894
M3 - Article
C2 - 36183964
VL - 790
SP - 136894
JO - Neuroscience letters
JF - Neuroscience letters
SN - 0304-3940
M1 - 136894
ER -
ID: 26348814