scholarly journals Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maya Lopez-Ichikawa ◽  
Ngan K. Vu ◽  
Amar Nijagal ◽  
Boris Rubinsky ◽  
Tammy T. Chang
Keyword(s):  
Cell Death ◽  
Innate Immune System ◽  
Tissue Injury ◽  
Irreversible Electroporation ◽  
Surgical Oncology ◽  
Innate Immune ◽  
Hepatic Progenitor Cells ◽  
Programmed Necrosis ◽  
Regenerative Repair

AbstractIrreversible electroporation (IRE) is a non-thermal tissue ablative technology that has emerging applications in surgical oncology and regenerative surgery. To advance its therapeutic usefulness, it is important to understand the mechanisms through which IRE induces cell death and the role of the innate immune system in mediating subsequent regenerative repair. Through intravital imaging of the liver in mice, we show that IRE produces distinctive tissue injury features, including delayed yet robust recruitment of neutrophils, consistent with programmed necrosis. IRE treatment converts the monocyte/macrophage balance from pro-inflammatory to pro-reparative populations, and depletion of neutrophils inhibits this conversion. Reduced generation of pro-reparative Ly6CloF4/80hi macrophages correlates with lower numbers of SOX9+ hepatic progenitor cells in areas of macrophage clusters within the IRE injury zone. Our findings suggest that neutrophils play an important role in promoting the development of pro-reparative Ly6Clo monocytes/macrophages at the site of IRE injury, thus establishing conditions of regenerative repair.

scholarly journals For Better or for Worse: A Look Into Neutrophils in Traumatic Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Sandra Zivkovic ◽  
Maryam Ayazi ◽  
Grace Hammel ◽  
Yi Ren
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Innate Immune System ◽  
Tissue Injury ◽  
Innate Immune ◽  
Traumatic Spinal Cord Injury ◽  
Injured Spinal Cord ◽  
Cord Injury ◽  
Molecular Patterns

Neutrophils are short-lived cells of the innate immune system and the first line of defense at the site of an infection and tissue injury. Pattern recognition receptors on neutrophils recognize pathogen-associated molecular patterns or danger-associated molecular patterns, which recruit them to the destined site. Neutrophils are professional phagocytes with efficient granular constituents that aid in the neutralization of pathogens. In addition to phagocytosis and degranulation, neutrophils are proficient in creating neutrophil extracellular traps (NETs) that immobilize pathogens to prevent their spread. Because of the cytotoxicity of the associated granular proteins within NETs, the microbes can be directly killed once immobilized by the NETs. The role of neutrophils in infection is well studied; however, there is less emphasis placed on the role of neutrophils in tissue injury, such as traumatic spinal cord injury. Upon the initial mechanical injury, the innate immune system is activated in response to the molecules produced by the resident cells of the injured spinal cord initiating the inflammatory cascade. This review provides an overview of the essential role of neutrophils and explores the contribution of neutrophils to the pathologic changes in the injured spinal cord.

Role of Innate Immune System in Environmental Lung Diseases

2021 ◽  
Vol 21 (5) ◽  
Author(s):  
Marissa A. Guttenberg ◽  
Aaron T. Vose ◽  
Robert M. Tighe
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Lung Diseases ◽  
Innate Immune

scholarly journals Role of the Innate Immune System in Acute Viral Myocarditis

2009 ◽  
Vol 104 (3) ◽  
pp. 228-237 ◽  
Author(s):  
Chien-Hua Huang ◽  
Jesus G. Vallejo ◽  
George Kollias ◽  
Douglas L. Mann
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Viral Myocarditis ◽  
Innate Immune ◽  
Acute Viral Myocarditis

Role of the innate immune system in the development of chronic colitis

2002 ◽  
Vol 37 (S14) ◽  
pp. 38-42 ◽  
Author(s):  
Takanori Kanai ◽  
Ryoichi Iiyama ◽  
Takahiro Ishikura ◽  
Koji Uraushihara ◽  
Teruji Totsuka ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Chronic Colitis

scholarly journals The Zα2 domain of ZBP1 is a molecular switch regulating influenza-induced PANoptosis and perinatal lethality during development

2020 ◽  
Vol 295 (24) ◽  
pp. 8325-8330 ◽  
Author(s):  
Sannula Kesavardhana ◽  
R. K. Subbarao Malireddi ◽  
Amanda R. Burton ◽  
Shaina N. Porter ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Cell Death ◽  
Nucleic Acids ◽  
Influenza A Virus ◽  
Nlrp3 Inflammasome ◽  
Influenza A ◽  
Defense Responses ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Perinatal Lethality

Z-DNA-binding protein 1 (ZBP1) is an innate immune sensor of nucleic acids that regulates host defense responses and development. ZBP1 activation triggers inflammation and pyroptosis, necroptosis, and apoptosis (PANoptosis) by activating receptor-interacting Ser/Thr kinase 3 (RIPK3), caspase-8, and the NLRP3 inflammasome. ZBP1 is unique among innate immune sensors because of its N-terminal Zα1 and Zα2 domains, which bind to nucleic acids in the Z-conformation. However, the specific role of these Zα domains in orchestrating ZBP1 activation and subsequent inflammation and cell death is not clear. Here we generated Zbp1ΔZα2/ΔZα2 mice that express ZBP1 lacking the Zα2 domain and demonstrate that this domain is critical for influenza A virus–induced PANoptosis and underlies perinatal lethality in mice in which the RIP homotypic interaction motif domain of RIPK1 has been mutated (Ripk1mRHIM/mRHIM). Deletion of the Zα2 domain in ZBP1 abolished influenza A virus–induced PANoptosis and NLRP3 inflammasome activation. Furthermore, deletion of the Zα2 domain of ZBP1 was sufficient to rescue Ripk1mRHIM/mRHIM mice from perinatal lethality caused by ZBP1-driven cell death and inflammation. Our findings identify the essential role of the Zα2 domain of ZBP1 in several physiological functions and establish a link between Z-RNA sensing via the Zα2 domain and promotion of influenza-induced PANoptosis and perinatal lethality.

Sign in / Sign up

Export Citation Format

Share Document