title: Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.
abstract: Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Javid
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Zlotnikov
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Helena
authors.initials: H
authors.lastname: Pětrošová
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Tian Tian
authors.initials: TT
authors.lastname: Tang
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Bansal
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Rhodaba
authors.initials: R
authors.lastname: Ebady
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Maitry
authors.initials: M
authors.lastname: Parikh
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Mijhgan
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Sun
authors.affiliation: Mount Sinai Hospital/Research Institute, The Toronto Centre for Phenogenomics, 25 Orde Street, Toronto, Ontario, M5T 3H7, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Newbigging
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Yae Ram
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Marianna
authors.initials: M
authors.lastname: Santana Sosa
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Glogauer
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Tara J
authors.identifier: http://orcid.org/0000-0002-1751-5145
authors.initials: TJ
authors.lastname: Moriarty
mesh_terms: D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000473:pathology; D058491:Bacterial Load; D025065:Borrelia burgdorferi / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000209:etiology; D007113:Immunity, Innate; D015994:Incidence; D008193:Lyme Disease / Q000150:complications* / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050296:Microbial Viability / Q000276:immunology; D009205:Myocarditis / Q000209:etiology / Q000473:pathology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology