MSK
Search
- Page Path
- HOME > Search
Journal Article
- Pten gene deletion in intestinal epithelial cells enhances susceptibility to Salmonella Typhimurium infection in mice
- Cody Howe , Jonathon Mitchell , Su Jin Kim , Eunok Im , Sang Hoon Rhee
- J. Microbiol. 2019;57(11):1012-1018. Published online September 25, 2019
- DOI: https://doi.org/10.1007/s12275-019-9320-3
- 64 View
- 0 Download
- 9 Web of Science
- 9 Crossref
-
Abstract
- Although phosphatase and tensin homolog (PTEN) is typically considered a tumor-suppressor gene, it was recently suggested that PTEN regulates TLR5-induced immune and inflammatory responses in intestinal epithelial cells (IECs), suggesting an immunomodulatory function of PTEN in the gut. However, this alternative function of PTEN has not yet been evaluated in an in vivo context of protection against enteropathogenic bacteria. To address this, we utilized IECrestricted Pten knockout (PtenΔIEC/ΔIEC) and littermate Pten+/+ mice. These mice were subjected to the streptomycin-pretreated mouse model of Salmonella infection, and subsequently given an oral gavage of a low inoculum (2 × 104 CFU) of Salmonella enterica serovar Typhimurium (S. Typhimurium). This bacterial infection not only increased the mortality of PtenΔIEC/ΔIEC mice compared to Pten+/+ mice, but also induced deleterious gastrointestinal inflammation in PtenΔIEC/ΔIEC mice manifested by massive histological damage to the intestinal mucosa. S. Typhimurium infection upregulated pro-inflammatory cytokine production in the intestine of PtenΔIEC/ΔIEC mice compared to controls. Furthermore, bacterial loads were greatly increased in the liver, mesenteric lymph node, and spleen of PtenΔIEC/ΔIEC mice compared to controls. Together, these results suggest that IEC-restricted Pten deficiency renders the host greatly susceptible to Salmonella infection and support an immuneregulatory role of PTEN in the gut.
-
Citations
Citations to this article as recorded by
- Exploring Protein Functions of Gut Bacteriome and Mycobiome in Thai Infants Associated with Atopic Dermatitis Through Metaproteomic and Host Interaction Analysis
Thanawit Chantanaskul, Preecha Patumcharoenpol, Sittirak Roytrakul, Amornthep Kingkaw, Wanwipa Vongsangnak
International Journal of Molecular Sciences.2024; 25(24): 13533. CrossRef - QTL Mapping-Based Identification of Visceral White-Nodules Disease Resistance Genes in Larimichthys polyactis
Qian Li, Jiajie Zhu, Sifang Liu, Haowen Liu, Tianle Zhang, Ting Ye, Bao Lou, Feng Liu
International Journal of Molecular Sciences.2024; 25(20): 10872. CrossRef - Cannabinoid enhancement of lncRNA MMP25-AS1/MMP25 interaction reduces neutrophil infiltration and intestinal epithelial injury in HIV/SIV infection
Lakmini S. Premadasa, Eunhee Lee, Marina McDew-White, Xavier Alvarez, Sahana Jayakumar, Binhua Ling, Chioma M. Okeoma, Siddappa N. Byrareddy, Smita Kulkarni, Mahesh Mohan
JCI Insight.2023;[Epub] CrossRef - Regulator of RNase E activity modulates the pathogenicity of Salmonella Typhimurium
Jaejin Lee, Eunkyoung Shin, Ji-Hyun Yeom, Jaeyoung Park, Sunwoo Kim, Minho Lee, Kangseok Lee
Microbial Pathogenesis.2022; 165: 105460. CrossRef - Endoribonuclease-mediated control of hns mRNA stability constitutes a key regulatory pathway for Salmonella Typhimurium pathogenicity island 1 expression
Minho Lee, Minkyung Ryu, Minju Joo, Young-Jin Seo, Jaejin Lee, Hong-Man Kim, Eunkyoung Shin, Ji-Hyun Yeom, Yong-Hak Kim, Jeehyeon Bae, Kangseok Lee, William Navarre
PLOS Pathogens.2021; 17(2): e1009263. CrossRef - Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer
Yunna Lee, Elise L. Ma, Marisa Patel, Gayoung Kim, Cody Howe, Charalabos Pothoulakis, Yong Sung Kim, Eunok Im, Sang Hoon Rhee
International Journal of Molecular Sciences.2021; 22(3): 1043. CrossRef - Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor
Tianyu He, Xiaoyun Zhang, Jianyu Hao, Shigang Ding
Frontiers in Physiology.2021;[Epub] CrossRef - Phosphatase and Tensin Homolog (PTEN) of Japanese Flounder—Its Regulation by miRNA and Role in Autophagy, Apoptosis and Pathogen Infection
Wenrui Li, Xiaolu Guan, Li Sun
International Journal of Molecular Sciences.2020; 21(20): 7725. CrossRef - Chlorogenic Acid Promotes Autophagy and Alleviates Salmonella Typhimurium Infection Through the lncRNAGAS5/miR-23a/PTEN Axis and the p38 MAPK Pathway
Shirui Tan, Fang Yan, Qingrong Li, Yaping Liang, Junxu Yu, Zhenjun Li, Feifei He, Rongpeng Li, Ming Li
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
- Exploring Protein Functions of Gut Bacteriome and Mycobiome in Thai Infants Associated with Atopic Dermatitis Through Metaproteomic and Host Interaction Analysis
Research Support, Non-U.S. Gov't
- Immunological Responses Induced by asd and wzy/asd Mutant Strains of Salmonella enterica serovar Typhimurium in BALB/c Mice
- Hong Hua Piao , Vo Thi Minh Tam , Hee Sam Na , Hyun Ju Kim , Phil Youl Ryu , Soo Young Kim , Joon Haeng Rhee , Hyon E. Choy , Suhng Wook Kim , Yeongjin Hong
- J. Microbiol. 2010;48(4):486-495. Published online August 20, 2010
- DOI: https://doi.org/10.1007/s12275-010-0023-z
- 44 View
- 0 Download
- 9 Scopus
-
Abstract
- Attenuated bacteria have long been developed as vaccine candidates but can have some disadvantages, such as the potential for damage to immune organs due to insufficient clearance. To minimize these disadvantages, we generated Salmonella enterica serovar Typhimurium mutants SHJ2104 (asd::cm) and HTSaYA (wzy::km, asd::cm). The wzy gene codes for the O-antigen polymerase, which is involved in lipopolysaccharide (LPS) biosynthesis, and asd codes for aspartate ß- semialdehyde dehydrogenase, which participates in cell wall formation. The strains synthesized LPS with a short-chain length, and showed lower cytotoxicity and reduced intracellular proliferation in animal cells compared to wild-type bacteria. After oral infection, the mutants were cleared in immune tissues, including the Peyer’s patch, mesenteric lymph node, and spleen, within 5 days. The LD50 of the mutants in Balb/c mice was estimated to be 106 higher than wild-type bacteria when administered either via an oral or i.p. route, indicating that the two strains are highly attenuated. To compare the immune response to and protective effects of the mutants against wild-type bacterial infection, we inoculated the mutants into mice via an oral (1×1010 CFU) or i.p. (1×107 CFU) route once or twice at a two week interval. All immune responses, such as serum IgG and secretory IgA levels, cytokine production, and delayed hypersensitivity, were highly induced by two rounds of immunization. HTSaYA and SHJ2104 induced similar immune responses, and mice immunized with HTSaYA or SHJ2104 via an i.p. route were protected against wild-type Salmonella infection even at 100-fold of the LD50 (5×106 CFU). Taken together, these data indicate that HTSaYA and SHJ2104 could be developed as live attenuated Salmonella vaccine candidates.
First
Prev
TOP
