2. Academic Validation
  3. MCPIP-1-Mediated Immunosuppression of Neutrophils Exacerbates Acute Bacterial Peritonitis and Liver Injury

MCPIP-1-Mediated Immunosuppression of Neutrophils Exacerbates Acute Bacterial Peritonitis and Liver Injury

  • J Innate Immun. 2022 Oct 21;1-21. doi: 10.1159/000526784.
Jian Lin 1 2,  Zhanjun Lu 3,  Gengfeng Li 1,  Cui Zhang 1,  Huiying Lu 1,  Sheng Gao 4,  Ruixin Zhu 4,  Hailiang Huang 5,  Konrad Aden 6,  Jianhua Wang 7,  Yingzi Cong 8,  Huili Wu 9,  Zhanju Liu 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Shanghai Tenth People's Hospital of Tongji University School of Medicine, Shanghai, China.
  • 2 Department of Gastroenterology, Affiliated Hospital of Putian University, Putian, China.
  • 3 Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 5 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • 6 Department of Internal Medicine I, Institute of Clinical Molecular Biology, Christian-Albrechts-University, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
  • 7 Storr Liver Unit, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.
  • 8 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • 9 Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
PMID: 36273448 DOI: 10.1159/000526784
Abstract

Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1) is highly expressed in activated immune cells and negatively regulates immune responses, while the mechanisms underlying the immunoregulation of neutrophils in acute Bacterial infection and liver injury remain elusive. Here, we examined the role of MCPIP-1 in regulating neutrophil functions during acute Bacterial peritonitis and liver injury. Mice with myeloid cell-specific overexpression (McpipMye-tg) or knockout (McpipΔMye) of MCPIP-1 were generated. We found that Reactive Oxygen Species and myeloperoxidase production, formation of neutrophil extracellular traps, and migratory capacity were deficient in McpipMye-tg neutrophils but enhanced in McpipΔMye neutrophils. The recruitment of neutrophils and pathogen clearance were markedly suppressed in McpipMye-tg mice following intraperitoneal Infection with Salmonella typhimurium while intensified in McpipΔMye mice. Severe acute S. typhimurium-infected peritonitis and liver injury occurred in McpipMye-tg mice but were alleviated in McpipΔMye mice. RNA sequencing, RNA-binding protein immunoprecipitation and qPCR analysis revealed that MCPIP-1 downregulated the protective functions of neutrophils via degrading the mRNA of cold inducible RNA-binding protein. Consistently, MCPIP-1 was highly expressed in neutrophils of patients with acute infectious diseases, especially in those with liver injury. Collectively, we uncover that MCPIP-1 negatively regulates the Antibacterial capacities of neutrophils, leading to exacerbating severe acute Bacterial peritonitis and liver injury. It may serve as a candidate target for maintaining neutrophil homeostasis to control acute infectious diseases.

Keywords

Acute bacterial peritonitis; Bacterial infection; Liver injury; MCPIP-1; Neutrophils.

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