title: Defects in early cell recruitment contribute to the increased susceptibility to respiratory Klebsiella pneumoniae infection in diabetic mice.
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.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martinez
authors.affiliation: 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.
authors.forename: Natkunam
authors.initials: N
authors.lastname: Ketheesan
authors.affiliation: Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Martens
authors.affiliation: Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: West
authors.affiliation: 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.
authors.forename: Egil
authors.initials: E
authors.lastname: Lien
authors.affiliation: 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.
authors.forename: Hardy
authors.initials: H
authors.lastname: Kornfeld
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004198:Disease Susceptibility; D015870:Gene Expression; D007113:Immunity, Innate; D007710:Klebsiella Infections / Q000276:immunology* / Q000473:pathology*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009504:Neutrophils / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology*; D011971:Receptors, Immunologic / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D011971:Receptors, Immunologic
keywords: Diabetes; Klebsiella pneumoniae; Lung; Pneumonia