Gut-mediated macrophage pyroptosis increases vulnerability to sepsis during pregnancy. Chen et al.

Published: 20 December 2022| Version 1 | DOI: 10.17632/4zntcrby5d.1
Contributor:
Shenhai Gong

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(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.

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Southern Medical University

Categories

Pregnancy, Sepsis, Macrophage, Gut Microbiota

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