Extended Data Fig. 10: Efficient rescue of anxiety-induced immune dysfunction by MCT1 blockade.
From: AARS1 and AARS2 sense l-lactate to regulate cGAS as global lysine lactyltransferases
a, Schematic of RS model in vivo: cGASwt/wt and cGASKR/KR mice were non-treated (NT) or given RS, followed by behavioral test and HSV-1 infection. b, Measurement of L-lactate in serum of cGASwt/wt and cGASKR/KR mice given NT or RS (n = 12). c, Representative tracks (left) of cGASwt/wt and cGASKR/KR mice in open-field test (OFT) (n = 12) on day 8 after inducing RS model, as well as travel distance (middle-left), percentage of distance in center area (middle-right) and percentage of time spent in center (right). d, Representative tracks (left), the number of entries into the open arms (middle-left), time on open arms (middle-right) and the number of total entries into two arms (right) in elevated plus-maze (EPM) of NT and RS mice described as in a on day 8 (n = 12). e, ELISA of cGAMP (left) and IFN-β (middle) in the serum of mice as in a (n = 6). Plaque assay of HSV-1 titers (right) in the lung of cGASwt/wt and cGASKR/KR mice as in a (n = 6). f, Survival of mice (n = 10) as in a after HSV-1 infection. g, Wild-type mice were given NT or RS for seven consecutive days and treated with control vehicle or 50 mg/kg AZD3965 orally twice daily, followed by behavioral test and HSV-1 infection (5×108 PFU per mouse, tail intravenous injection). Representative tracks (left) of the above mice in open-field test (OFT) (n = 12) on day 8 after inducing RS model, as well as travel distance (middle-left), percentage of distance in center area (middle-right) and percentage of time spent in center (right). h, Related to Fig. 5i, body weight of mice during AZD3965 treatment (n = 12). i, Related to Fig. 5k, immunoblot (IB) of the total cell lysate (TCL) and immunoaffinity purified proteins in PBMCs (left) or BMDMs (right) isolated from mice. Wild-type mice were given NT or RS for seven consecutive days and treated with control vehicle or 50 mg/kg AZD3965 orally twice daily, followed by behavioral test and HSV-1 infection (5×108 PFU per mouse, tail intravenous injection). j, ELISA of cGAMP (left) and qPCR analysis of Ifnb1 mRNA (right) in the lung, spleen and liver of mice as in g (n = 6 animals per group). Data are representative of at least three independent experiments (b-j). Mean ± s.d., statistical analysis was performed using two-tailed Student’s t-test (e, j), Dunnett’s test (b-d, g), Log-rank test (f) or two-way ANOVA analysis (h). Supplementary Fig. 1 shows full gels.
