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Published on: January 8, 2020
VDUP1 exacerbates bacteremic shock in mice infected with Pseudomonas aeruginosa
Zheng-Hao Piao1, Mi Sun Kim, Mira Jeong
1Immunotherapy Research Center, Korea Research of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea.
Abstract:
Vitamin-D3 upregulated protein-1 (VDUP1) is a stress response protein. Pseudomonas aeruginosa (P. aeruginosa) infection is a leading cause of death. Mice infected with live P. aeruginosa exhibit significantly decreased VDUP1 expression. However, the function of VDUP1 during P. aeruginosa-induced mouse bacteremic shock is unknown. To address the function of VDUP1 in P. aeruginosa-infected mice, we constructed a bacteremic shock model wherein both wild-type and VDUP1-deficient mice were infected intra-peritoneally with live P. aeruginosa. We found that VDUP1-deficient mice were more resistant to P. aeruginosa-induced bacteremic shock than wild-type mice, as shown by the increased survival, accelerated bacterial clearance and suppression of cytokine overproduction of the VDUP1-deficient mice. VDUP1 promoted the recruitment of neutrophils into the peritoneal cavities of infected mice. VDUP1 impeded the phagocytosis of non-opsonized P. aeruginosa via phosphatidylinositide 3-kinase (PI3K) pathway in macrophages. P. aeruginosa infection induced the generation of reactive oxygen species (ROS), and the increased production of ROS by the peritoneal cells of VDUP1-deficient mice was advantageous in clearing the bacteria. Overall, VDUP1 aggravates bacteremic shock; thus, VDUP1 can be considered a target molecule for the inhibition of P. aeruginosa-induced bacteremic shock.
Insights
Vitamin-D3 upregulated protein-1 (VDUP1) aggravates Pseudomonas aeruginosa-induced bacteremic shock. VDUP1-deficient mice show increased survival and bacterial clearance, suggesting VDUP1 as a therapeutic target.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Vitamin-D3 upregulated protein-1 (VDUP1) is a stress response protein.
- Pseudomonas aeruginosa (P. aeruginosa) infection is a significant cause of mortality.
- The role of VDUP1 in P. aeruginosa-induced bacteremic shock remains unclear.
Purpose of the Study:
- To investigate the function of VDUP1 in P. aeruginosa-induced bacteremic shock in a mouse model.
- To determine if VDUP1 deficiency impacts resistance to P. aeruginosa infection.
Main Methods:
- Construction of a bacteremic shock model using wild-type and VDUP1-deficient mice.
- Intraperitoneal infection with live P. aeruginosa.
- Assessment of survival rates, bacterial clearance, cytokine production, neutrophil recruitment, and macrophage phagocytosis.
Main Results:
- VDUP1-deficient mice exhibited enhanced resistance to P. aeruginosa-induced bacteremic shock.
- Increased survival, accelerated bacterial clearance, and suppressed cytokine overproduction were observed in VDUP1-deficient mice.
- VDUP1 promoted neutrophil recruitment and impaired macrophage phagocytosis of P. aeruginosa via the PI3K pathway.
- Increased reactive oxygen species (ROS) production in VDUP1-deficient mice aided bacterial clearance.
Conclusions:
- VDUP1 exacerbates P. aeruginosa-induced bacteremic shock.
- Targeting VDUP1 may offer a therapeutic strategy for inhibiting P. aeruginosa-induced bacteremic shock.
