Fig 2: The hCD11b mouse is susceptible to MRSA infection.(A and B) WT and hCD11b mice were infected intravenously with ~3 × 106 CFU of WT USA300 strain LAC or an isogenic ΔlukAB LAC strain. Three days after infection, % of mice with detectable CFUs in the liver was determined (A). Statistical significance was determined by chi-square test (**P < 0.01). (B) CFUs in the livers were also quantified. Data are represented as the average of three independent experiments with 15 total mice per group. Statistical significance was determined by one-way ANOVA (**P < 0.01 and *P < 0.05). (C) WT and hCD11b mice were infected intravenously with 1 × 107 ΔlukAB::p LAC or ΔlukAB::plukAB LAC. One day after infection, CFUs in the livers were quantified. Data are represented as the average of two independent experiments with 10 total mice per group. Statistical significance was determined by one-way ANOVA (*P < 0.05). (D and E) hCD11b mice were infected intravenously with 1 × 108 CFU of WT LAC or an isogenic ΔlukAB LAC strain. (D) CFUs in the livers and kidneys 1 day after infection. (E) Tissue homogenates from (D) were also used to quantify LukAB. Data are represented as the average of three independent experiments with 15 total mice per group. Statistical significance was determined by one-way ANOVA (**P < 0.01). See also fig. S4. (F) WT mice were infected with S. aureus intravenously. One day after infection, the % Ly6G+ CD11b+ PMNs out of the total CD45% leukocytes were quantified. Data are represented as the average of two independent experiments with six total mice per group. Statistical significance was determined by one-way ANOVA (***P < 0.001).

Fig 3: Loss of Cemip Enhances Reactive Adipogenesis(A) Representative histological images of skin from mice at day 0 and 3 days after infection with S. aureus. Tissue was stained with H&E. Brackets delineate dermal region occupied by adipocytes. Scale bar, 50 μm.(B) Quantification of the adipose tissue thickness indicated scale bar (n = 8 for control and Cemip−/− infection mice/group).(C-E) qRT-PCR of the relative abundance of transcripts for (C) Pref1, (D) PPARγ, and (E) Adipoq as normalized to β-actin (n = 4 for normal condition, n = 8 for infection mice/group).(F) Flow cytometry analysis of single-cell suspensions from the skin showing expression of PEGFRα from control, Cemip−/−, control infection, and Cemip−/− infection. Cells were gated on CD31-negative, CD45-negative, and SCA-1-positive.(G) Statistical comparison of the percentages of the cells in the indicated gates shown in (F).All error bars indicate mean ± SEM. *p < 0.05, **p < 0.01, and ***p < 0.001 (t test).

Fig 4: Twelve-week HFD reduced local cardiac inflammation. (A) Representative flow cytometry scatter plots and quantitative data for CD45+ leukocytes in the heart of ND- and HFD-treated mice 7 days after MI. (B,C) Representative flow cytometry scatter plots and quantitative data for Ly6G+ neutrophils in the heart (B) and spleen (C) of ND- and HFD-treated mice 7 days after MI. (D) Representative flow cytometry scatter plots and quantitative data for CD3−CD64+ macrophages and its subsets CD206- M1 and CD206+ M2 macrophages in the heart of ND- and HFD-treated mice 7 days after MI. (E) Proportion of M1 and M2 in the heart of ND- and HFD-treated mice 7 days after MI. (F) Expression levels of Il1b and Il6 in the infarcted region 7 days after MI as determined by reverse-transcription quantitative polymerase chain reaction. N=6 to 7/group. All error bars denote the mean ± SEM. *P<0.05; **P<0.01; ***P<0.001; ns, not significant. ND, normal diet; HFD, high-fat diet; SSC, side scatter; FSC, forward scatter; MI, myocardial infarction; SEM, standard error of mean.

Fig 5: Evaluation of the wound healing process treated with ECM scaffolds.a Workflow for evaluating large-scale wound healing. b Surgical processes for skin splinted excisional wound model. c Residual wound area at 3, 5, 7, 14, and 28 days, black dashed circles denoting the original wound area. d corresponding analysis of residual wound (Data are presented as mean ± SD, n = 4 biologically independent samples, two-tailed t-test, Day3 **p = 0.002; Day5 p = 0.104; Day7 **p = 0.001; Day14 ***p = 0.000444). e Representative H&E images of two groups at 7, 14, 21, and 28 days. f Quantitative evaluation of the gap width of neo-epithelium (Data are presented as mean ± SD, n = 4 biologically independent samples, two-tailed t-test, Day7 **p = 0.002; Day14 *p = 0.011). g Representative IF images of nascent HFs within the ECM_LW group, stained for KRT17 (green) and TWIST2 (red), Ki67 (red), and SCD1 (green), respectively. Abbreviations: HF, hair follicle; HG, hair germ; Dc, dermal condensate; SG, sebaceous gland. h Histologic quantification of de novo HFs on POD28 (Data are presented as mean ± SD, n = 5 biologically independent samples, two-tailed t-test, ***p = 0.000141). i Bulk-RNA sequencing analysis of ECM_LW versus Ctrl_LW mice on POD7 (n = 3 for each group). Heatmap (left) showing hierarchical clustering of differentially expressed genes (p value < 0.05 & |log2FC | > 1) between two groups, and corresponding gene set enrichment analysis (right) showing the enriched terms in ECM_LW (top) versus Ctrl_LW (bottom) groups. j Proportions of T cells (CD45+CD3+) and macrophages (CD45+CD3-F4/80+CD68+) cell populations in the wound environment on POD7, determined by flow cytometry (% = the number of target cells / the number of all single live cells) (Data are presented as mean ± SD, n = 3 biologically independent samples, two-tailed t-test, T cells *p = 0.013; Macrophages *p = 0.016). p value: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.