Endothelial Specific HSPA12B Plays a Critical Role in Maintaining Hepatic Kupffer Cell Bacterial Clearance
Location
Culp Room 217
Start Date
4-6-2022 1:45 PM
End Date
4-6-2022 2:00 PM
Faculty Sponsor’s Department
Surgery
Name of Project's Faculty Sponsor
Xiaohui Wang
Competition Type
Non-Competitive
Type
Boland Symposium
Project's Category
Infectious Diseases
Abstract or Artist's Statement
Sepsis is defined as a life-threatening disease that is characterized by multiple organ dysfunction caused by an uncontrolled host response to an infection. Hepatic dysfunction contributes to sepsis-induced mortality and morbidity. Hepatic Kupffer cells are a first-line defense in the clearance of bacteria or bacterial products, thus limiting the spread of the infection. We have previously shown that endothelial cell-specific HSPA12B prevents sepsis-induced multiple organ injury and mortality. However, there is no data available on the role of endothelial cell HSPA12B in hepatic (i.e. Kupffer cell) clearance of bacteria from the blood. To address this important question, we administered 5x107 E.coli-GFP to endothelial-specific HSAP12B deficient (Hspa12B ECKO) and wild type (WT) mice by i.v injection. Twenty minutes after injection, we collected blood specimens and harvested liver tissues for analysis of bacterial load in peripheral blood by flow cytometry and in the livers by immunofluorescence staining. Flow cytometric analysis showed that there was a significantly greater bacterial burden in the peripheral blood from Hspa12B ECKO mice than in WT mice. Immunofluorescence staining of liver tissues shows that there were fewer bacteria uptaken by hepatic Kupffer cells in Hspa12B ECKO mice, compared with WT mice. To investigate whether endothelial cell HSPA12B influenced Kupffer cell survival in the liver tissue, we induced polymicrobial sepsis in Hspa12B ECKO and WT mice and examined Kupffer cell numbers by F4/80 immunostaining. We observed that endothelial cell HSPA12B deficiency exacerbates sepsis-induced loss of Kupffer cells. These data suggest that endothelial cell HSPA12B is required for maintaining Kupffer cell numbers and regulating Kupffer cell bacterial uptake and clearance. βglucan can induce the trained immune phenotype. We examined whether β-glucan could improve Kupffer cell function and attenuate sepsis-induced mortality in Hspa12B ECKO mice. We treated Hspa12B ECKO mice with β-glucan (1mg/Kg) seven days before the induction of sepsis. We found that β-glucan treatment significantly attenuates sepsis-induced Kupffer cell loss and mortality. We conclude that endothelial-specific HSPA12B influences Kupffer cell survival in the liver and regulates Kupffer cell bacterial uptake. We also found that innate immune training can enhance Kupffer cell function in Hspa12B ECKO.
Endothelial Specific HSPA12B Plays a Critical Role in Maintaining Hepatic Kupffer Cell Bacterial Clearance
Culp Room 217
Sepsis is defined as a life-threatening disease that is characterized by multiple organ dysfunction caused by an uncontrolled host response to an infection. Hepatic dysfunction contributes to sepsis-induced mortality and morbidity. Hepatic Kupffer cells are a first-line defense in the clearance of bacteria or bacterial products, thus limiting the spread of the infection. We have previously shown that endothelial cell-specific HSPA12B prevents sepsis-induced multiple organ injury and mortality. However, there is no data available on the role of endothelial cell HSPA12B in hepatic (i.e. Kupffer cell) clearance of bacteria from the blood. To address this important question, we administered 5x107 E.coli-GFP to endothelial-specific HSAP12B deficient (Hspa12B ECKO) and wild type (WT) mice by i.v injection. Twenty minutes after injection, we collected blood specimens and harvested liver tissues for analysis of bacterial load in peripheral blood by flow cytometry and in the livers by immunofluorescence staining. Flow cytometric analysis showed that there was a significantly greater bacterial burden in the peripheral blood from Hspa12B ECKO mice than in WT mice. Immunofluorescence staining of liver tissues shows that there were fewer bacteria uptaken by hepatic Kupffer cells in Hspa12B ECKO mice, compared with WT mice. To investigate whether endothelial cell HSPA12B influenced Kupffer cell survival in the liver tissue, we induced polymicrobial sepsis in Hspa12B ECKO and WT mice and examined Kupffer cell numbers by F4/80 immunostaining. We observed that endothelial cell HSPA12B deficiency exacerbates sepsis-induced loss of Kupffer cells. These data suggest that endothelial cell HSPA12B is required for maintaining Kupffer cell numbers and regulating Kupffer cell bacterial uptake and clearance. βglucan can induce the trained immune phenotype. We examined whether β-glucan could improve Kupffer cell function and attenuate sepsis-induced mortality in Hspa12B ECKO mice. We treated Hspa12B ECKO mice with β-glucan (1mg/Kg) seven days before the induction of sepsis. We found that β-glucan treatment significantly attenuates sepsis-induced Kupffer cell loss and mortality. We conclude that endothelial-specific HSPA12B influences Kupffer cell survival in the liver and regulates Kupffer cell bacterial uptake. We also found that innate immune training can enhance Kupffer cell function in Hspa12B ECKO.