Impaired immune response and barrier function in GSPD-1-deficient C. elegans infected with Klebsiella pneumoniae

• Published in: Current research in microbial sciences 2023-01, Vol.4, p.100181-100181, Article 100181
• Main Authors: Yang, Wan-Hua, Chen, Po-Hsiang, Chang, Hung-Hsin, Kwok, Hong Luen, Stern, Arnold, Soo, Po-Chi, Chen, Jiun-Han, Yang, Hung-Chi
• Format: Article
• Language: English
• Subjects: Bacterial colonization; GSPD-1 C. elegans; Klebsiella pneumoniae; Research Paper; Tight junction
• ISSN: 2666-5174; 2666-5174
• DOI: 10.1016/j.crmicr.2023.100181

•Lack of GSPD-1 increased sensitivity to the infection of K. pneumoniae in C. elegans.•The innate immune response was the most important pathway affected by GSPD-1 revealed by RNAseq.•GSPD-1 maintained tight junction and intestinal barrier integrity.•GSPD-1 enhanced innate immunity though regulating the antimicrobial effector, lysozymes.•G6PD-deficient human cell culture recapitulated the defective immune response. gspd-1-RNAi knockdown Caenorhabditis elegans was used as an immune-compromised model to investigate the role of G6PD in host-pathogen interactions. A shorted lifespan, increased bacterial burden and bacterial translocation were observed in gspd-1-knockdown C. elegans infected with Klebsiella pneumoniae (KP). RNAseq revealed that the innate immune pathway, including clc-1 and tsp-1, was affected by gspd-1 knockdown. qPCR confirmed that tight junction (zoo-1, clc-1) and immune-associated genes (tsp-1) were down-regulated in gspd-1-knockdown C. elegans and following infection with KP. The down-regulation of antimicrobial effector lysozymes, including lys-1, lys-2, lys-7, lys-8, ilys-2 and ilys-3, was found in gspd-1-knockdown C. elegans infected with KP. Deletion of clc-1, tsp-1, lys-7, and daf-2 in gspd-1-knockdown C. elegans infected with KP abolished the shorten lifespan seen in the Mock control. GSPD-1 deficiency in C. elegans resulted in bacterial accumulation and lethality, possibly due to a defective immune response. These findings indicate that GSPD-1 has a protective role in microbial defense in C. elegans by preventing bacterial colonization through bacterial clearance. [Display omitted]