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

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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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 IEC-restricted Pten knockout (PtenΔIEC/ΔIEC) and littermate Pten+/+ mice. These mice were subjected to the streptomycin-pre-treated 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 up-regulated 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 immune-regulatory role of PTEN in the gut.

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Acknowledgements

This research was supported by grants from Oakland University and the National Institutes of Health (DK079015, S.H.R) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1A2C1010536 to E.I.).

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Authors and Affiliations

  1. Department of Biological Sciences, Oakland University, Rochester, Michigan, 48309, USA

    Cody Howe, Jonathon Mitchell, Su Jin Kim, Eunok Im & Sang Hoon Rhee

  2. College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea

    Su Jin Kim & Eunok Im

  3. Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA

    Sang Hoon Rhee

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  1. Cody Howe
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  2. Jonathon Mitchell
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Correspondence to Sang Hoon Rhee.

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Howe, C., Mitchell, J., Kim, S.J. et al. Pten gene deletion in intestinal epithelial cells enhances susceptibility to Salmonella Typhimurium infection in mice. J Microbiol. 57, 1012–1018 (2019). https://doi.org/10.1007/s12275-019-9320-3

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