Susceptibility of aging mice to listeriosis: Role of anti-inflammatory responses with enhanced Treg-cell expression of CD39/CD73 and Th-17 cells

Int J Med Microbiol. 2020 Feb;310(2):151397. doi: 10.1016/j.ijmm.2020.151397. Epub 2020 Jan 16.

Abstract

Foodborne Listeria monocytogenes (Lm) causes serious illness and death in immunosuppressed hosts, including the elderly population. We investigated Lm susceptibility and inflammatory cytokines in geriatric mice. Young-adult and old mice were gavaged with a Lm strain Lmo-InlAm. Tissues were assayed for Lm burden and splenocytes were analyzed for Th1/Th2/Th17/Treg responses and expression of CD39 and CD73. Old Lm-infected mice lost body-weight dose-dependently, had higher Lm colonization, and showed higher inflammatory responses than Lm-infected young-adult mice. After infection, IL-17 levels increased significantly in old mice whereas IFN-γ levels were unchanged. Levels of IL-10 and Treg cells were increased in infected old mice as compared to infected young-adult mice. Age-dependent enhanced expression of CD39/CD73 was observed in purified Treg prior to infection, suggesting increased baseline adenosine production in old mice. Lm lysate-treated splenocytes from older mice produced significantly higher levels of IL-10, IL17, and IL-1β, produced less IFN-γ and IL-2, and proliferated less than splenocytes from young-adult mice. Data suggests that older mice maybe more susceptible to Lm infection due to an imbalance of Th cell responses with disproportionate and persistent anti-inflammatory responses. Lm infection enhanced differentiation of proinflammatory Th17 cells, which may also exacerbate pathological responses during listeriosis.

Keywords: Aging; CD39/CD73; IFN-γ; IL-17; Listeria monocytogenes; Treg cells.

MeSH terms

  • 5'-Nucleotidase / genetics*
  • 5'-Nucleotidase / immunology
  • Age Factors
  • Aging*
  • Animals
  • Anti-Inflammatory Agents
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Apyrase / genetics*
  • Apyrase / immunology
  • Cytokines / immunology
  • Female
  • Inflammation
  • Interleukin-17 / immunology
  • Listeriosis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*

Substances

  • Anti-Inflammatory Agents
  • Antigens, CD
  • Cytokines
  • Interleukin-17
  • 5'-Nucleotidase
  • Apyrase
  • CD39 antigen