Microglial response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice after systemic stimulation with Escherichia coli. (1st November 2022)

• Record Type: Journal Article
• Authors: Hoogland, Inge C.M.; Yik, Jutka; Westhoff, Dunja; Engelen-Lee, Joo-Yeon; Valls Seron, Merche; Man, Wing-Kit; Houben-Weerts, Judith H.P.M.; Tanck, Michael W.; van Westerloo, David J.; van der Poll, Tom; van Gool, Willem A.; van de Beek, Diederik
• Is Part Of: Neuroscience letters. Volume 790(2022)
• Publication Date: 2022-11-01
• Subjects: 7-AAD 7-amino-actinomycin D -- A20 deubiquitinase protein A20 -- ADP adenosine diphosphate -- APC allophycocyanin -- ATP adenosine triphosphate -- °C degrees Celsius subcomponent q -- CA1 hippocampal Cornu Ammonis1 -- CD11b cluster of differentiation 11b -- CD14 cluster of differentiation 14 -- CD16 cluster of differentiation 16 -- CD32 cluster of differentiation 32 -- CD45 cluster of differentiation 45 -- cDNA complementary deoxyribonucleic acid -- CFU colony-forming units -- CI confidence interval -- CNS central nervous system -- CSF cerebral spinal fluid -- deltaCt delta cycle threshold -- E. coli Escherichia coli -- GABA gamma-aminobutyric acid -- geoMFI's geometric means -- GFAP glial fibrillary acidic protein -- GKN-BSA glucose-potassium-sodium -- HE hematoxylin and eosin -- HMGB1 high-mobility group 1 -- Iba-1 ionized calcium-binding adaptor molecule 1 -- IL-1β interleukin 1 beta -- IL-6 interleukin 6 -- IL-12 interleukin 12 -- IQR interquartile range -- IVC individually ventilated cages -- LB Luria-Bertani medium -- LPS lipopolysaccharide -- MAPK1 mitogen-activated protein kinase 1 -- MCP-1 monocyte chemotactic protein 1 -- M-CSF macrophage colony-stimulating factor -- mRNA messenger ribonucleic acid -- NoNo Non-POU-domain containing octamer binding protein -- PBS phosphate buffered saline -- PE phycoerythrin -- PerCP peridinin-chlorophyll-protein -- qPCR quantitative polymerase chain reaction -- RNA ribonucleic acid -- SOCS1 suppressor of cytokine signaling 1 -- TGF-β transforming growth factor beta -- TLR Toll-like receptor -- TLR-2 Toll-like receptor 2 -- TNF-α tumor necrosis factor alpha; Microglia -- Microglial activation -- Systemic infection -- Escherichia coli -- Neuro-inflammation -- Triggering receptor expressed on myeloid cells 2 -- TREM2 -- Knock-out -- Mouse model; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2022.136894
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Loss of function of TREM2 during systemic infection leads to an increased number of microglial cells in thalamus after inoculation . Loss of function of TREM2 during systemic infection does not lead to increased expression of pro-inflammatory genes in the brain. The role of TREM2 in the neuro-inflammatory response following systemic infection appears to be limited in our experiments. Abstract: 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-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.