Gut-mediated macrophage pyroptosis increases vulnerability to sepsis during pregnancy. Chen et al.
Description
(1A–1D) The cytokine and chemokine mRNAs in BALF (A), liver (B), kidney (C) and lung (D) from CLP mice. n=5-12. (2A, 2B) Bacterial load in cecal content and HE staining of liver, kidney and lung from ABX treated-mice. (2C-2F) The cytokine and chemokine mRNAs in PLF (C), liver (D), kidney (E), and lung (F) from ABX-pretreated pregnant and nonpregnant CLP mice. n=3-7. (3A-3D) Venn diagram comparing the shared genera in gut microbiome of donors and recipient mice. (3E, 3F) Plasma ALT, AST and Cr in microbiota-recipient mice. (3G, 3H) HE staining of liver, kidney, and lung from microbiota-recipient mice. (3I, 3J) HE staining of liver, kidney, and lung from septic recipient mice. (3K, 3L) The percentage of CD11b+ cells in the lung from septic recipient mice. (3M) The cytokine and chemokine mRNAs in PLF from septic recipient mice. n=4-18. (4A–4E) The cytokine and chemokine mRNAs in PLF (A), BALF (B), liver (C), kidney (D), and lung (E) from septic recipient mice. n=6-9. (5A-5D) Alpha diversity and abundance of gut microbiota in pregnant and nonpregnant individuals. (5E) Heatmap for cecal metabolites from pregnant and nonpregnant mice. (5F) Genome map circular view of P. merdae. n=8-42. (6A-6J) The percentages of macrophages and neutrophils in PLF from nonpregnant and pregnant septic mice, ABX-pretreated septic mice and septic recipient mice. n=6-9. (7A-7C) The percentages of lymphocytes in PLF of nonpregnant and pregnant septic mice, ABX-pretreated septic mice and septic recipient mice. (7D-7G) The percentages of monocytes and neutrophils in blood of pregnant and nonpregnant mice, FMT-recipient mice with P. aeruginosa (PAE) infection. n=6-8. (8A-8J) The percentages of monocytes and neutrophils in blood of nonpregnant and pregnant septic mice, ABX-pretreated septic mice and septic recipient mice. (8K, 8L) The percentages of monocytes and neutrophils in blood of septic recipient mice. FMT was performed in germ-free mice. n=4-8. (9A-9C) Flow-cytometric enumeration of macrophages in PLF from nonpregnant and pregnant septic mice, ABX-pretreated mice and septic recipient mice. (9D) The percentages of macrophages in PLF of CLP mice treated with ferrostatin-1 (10 mg/kg), necrostatin-1 (1.65 mg/kg), or Z-DEVD-FMK (8 mg/kg). (9E, 9F) Transcriptomic analysis of LPS plus ATP treated-BMDMs with or without FMN treatment. (9G–9I) The expression of p20 of caspase1 and N-terminus of GSDMD. After priming with LPS for 2 h, BMDMs were treated with FMN for an additional 2 h, in the presence or absence of VX765 (50 μM), which was followed by triggering with 5 mM ATP for 30 min. n=3-6. (10A) Proteomic analysis of LPS plus ATP-treated BMDMs with or without FMN treatment. (10B, 10C) The expression of hnRNPUL2 in BMDMs transfected with siRNA targeting hnRNPUL2. (10D) A docking model showing the interactions between FMN and hnRNPUL2. (10E) The mRNA of hnRNPUL2 in mice subjected to injection of AAV9-hnRNPUL2. n=3-8. *p<0.05 by two-tailed unpaired t-test.