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  3. Defects in early cell recruitment contribute to the increased susceptibility to respiratory Klebsiella pneumoniae infection in diabetic mice

Defects in early cell recruitment contribute to the increased susceptibility to respiratory Klebsiella pneumoniae infection in diabetic mice

  • Microbes Infect. 2016 Oct;18(10):649-655. doi: 10.1016/j.micinf.2016.05.007.
Nuria Martinez 1,  Natkunam Ketheesan 2,  Gregory W Martens 1,  Kim West 1,  Egil Lien 3,  Hardy Kornfeld 4
Affiliations

Affiliations

  • 1 Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • 2 Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA; Australian Institute of Tropical Health and Medicine, James Cook University, Queensland 4811, Australia.
  • 3 Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA; CEMIR, Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.
  • 4 Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: Hardy.Kornfeld@umassmed.edu.
PMID: 27256462 DOI: 10.1016/j.micinf.2016.05.007
Abstract

Diabetes is associated with increased susceptibility to Klebsiella pneumoniae and poor prognosis with Infection. We demonstrate accelerated mortality in mice with streptozotocin-induced diabetes following tracheal instillation of K. pneumoniae. Diabetic mice recruited fewer granulocytes to the alveolar airspace and had reduced early production of CXCL1, CXCL2, IL-1β and TNF-α following tracheal instillation of K. pneumoniae-lipopolysaccharide. Additionally, TLR2 and TIRAP expression following K. pneumoniae-lipopolysaccharide exposure was decreased in hyperglycemic mice. These findings indicate that impaired innate sensing and failure to rapidly recruit granulocytes to the site of Infection is a mechanism for diabetic susceptibility to respiratory K. pneumoniae Infection.

Keywords

Diabetes; Klebsiella pneumoniae; Lung; Pneumonia.

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