Extended Data Fig. 6: Blocking CCR2 reduces MDM level in the brain of Trem2^-/-5xFAD mice.

(a,b) Locomotor activity measured by total distance that each mouse moved (cm; mean ± SEM) (a), and anxiety measured by time (sec; mean ± SEM) spent in the center of the arena (b), both measured on the habituation phase (day 1) of the NOR task (Trem2^−/−WT n=5, Trem2^−/−5xFAD/IgG2b n=5, Trem2^−/−5xFAD/anti-PD-L1 n=7, Trem2^−/−5xFAD/anti-PD-L1 + anti-CCR2 n=8), analyzed using one-way ANOVAs ([a] F_(3,21)=0.4152, p=0.744; [b] F_(3,21)=0.323, p=0.8). (c) ELISA assessment of hippocampal Aβ_1-42 Triton X-100-soluble from anti-PD-L1 (n=7; 5 females, 2 males) and anti-PD-L1+ anti-CCR2 (n=9; 6 females, 3 males) treated Trem2^−/−5xFAD mice was analyzed using one-tailed Student’s t test: t₍₁₄₎=0.126, p=0.45); data derived from 3 cohorts of mice, pooled together after normalization. (d) Flow cytometry plots demonstrating the gating strategy for live single MDM cells in Trem2^−/−5xFAD brains. (e) Quantification (presented as mean ± SEM) of MDM (CD45+CD11b+CD44+Ly6G-CD38-) in Trem2^−/−5xFAD treated with IgG, anti-PD-L1 or anti-PD-L1 together with anti-CCR2 and untreated Trem2^−/−WT; n/group=5. One-way ANOVA yielded a significant main effect (F_(3,16)=4.629, p=0.016, R²=0.4647) which was followed by Fisher’s LSD tests. ^# relates to the comparison between anti-PD-L1 and IgG2b; ^Φ relates to the comparison with WT; n.s - not significant.^,#,Φ indicate p < 0.05.