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

doi:10.1007/s12275-019-9320-3

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Pten gene deletion in intestinal epithelial cells enhances susceptibility to Salmonella Typhimurium infection in mice: Cody Howe ¹, Jonathon Mitchell ¹, Su Jin Kim ^1,2, Eunok Im ^1,2, Sang Hoon Rhee ^1,3; Journal of Microbiology 2019;57(11):1012-1018.
DOI: https://doi.org/10.1007/s12275-019-9320-3
Published online: September 25, 2019

¹Department of Biological Sciences, Oakland University, Rochester, Michigan, 48309, USA, ²College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea, ³Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, CA, 90095, USA¹Department of Biological Sciences, Oakland University, Rochester, Michigan, 48309, USA, ²College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea, ³Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, CA, 90095, USA

Received: 27 June 2019 • Revised: 30 July 2019 • Accepted: 30 July 2019

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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.

Keywords: immune responses;intestinal epithelial cells;Pten;Toll-like receptor

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Pten gene deletion in intestinal epithelial cells enhances susceptibility to Salmonella Typhimurium infection in mice

J. Microbiol. 2019;57(11):1012-1018. Published online September 25, 2019

DOI: https://doi.org/10.1007/s12275-019-9320-3

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