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

Wan-Hua Yang; Po-Hsiang Chen; Hung-Hsin Chang; Hong Luen Kwok; Arnold Stern; Po-Chi Soo; Jiun-Han Chen; Hung-Chi Yang

doi:10.1016/j.crmicr.2023.100181

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

Curr Res Microb Sci. 2023 Jan 27:4:100181. doi: 10.1016/j.crmicr.2023.100181. eCollection 2023.

Authors

Wan-Hua Yang¹, Po-Hsiang Chen², Hung-Hsin Chang³, Hong Luen Kwok³, Arnold Stern⁴, Po-Chi Soo⁵, Jiun-Han Chen³, Hung-Chi Yang³

Affiliations

¹ Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Hsinchu Branch, Hsinchu, Taiwan.
² Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
³ Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu 30041, Taiwan.
⁴ Grossman School of Medicine, New York University, New York, NY, USA.
⁵ Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien, Taiwan.

Abstract

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.

Keywords: Bacterial colonization; GSPD-1 C. elegans; GSPD-1, Glucose Six (6) Phosphate Dehydrogenase; Klebsiella pneumoniae; NADPH, Nicotinamide adenine dinucleotide phosphate; Tight junction.