Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen

PLoS One. 2016 Jun 24;11(6):e0158019. doi: 10.1371/journal.pone.0158019. eCollection 2016.

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.

MeSH terms

  • Animals
  • Arthritis / etiology
  • Arthritis / pathology
  • Bacterial Load
  • Borrelia burgdorferi / immunology*
  • Cytotoxicity, Immunologic
  • Diabetes Mellitus, Experimental
  • Disease Models, Animal
  • Female
  • Humans
  • Hyperglycemia / complications*
  • Hyperglycemia / etiology
  • Immunity, Innate*
  • Incidence
  • Lyme Disease / complications*
  • Lyme Disease / immunology*
  • Lyme Disease / microbiology
  • Male
  • Mice
  • Mice, Knockout
  • Microbial Viability / immunology
  • Myocarditis / etiology
  • Myocarditis / pathology
  • Neutrophil Activation / immunology
  • Neutrophils / immunology*
  • Neutrophils / microbiology

Grant support

This study was funded by National Research Fund for Tick Borne Diseases (TJM); Canadian Institutes of Health Research (CIHR) operating grants: MOP-11959 (TJM) and TO-122068 (MG); CIHR Bhagirath Singh Award: ICS-12398 (TJM); Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant: RGPIN 401 (TJM); Banting Research Foundation (TJM); University of Toronto Faculty of Dentistry Bertha Rosenstadt Endowment Fund (TJM) and Enrichment Endowment Fund (TJM); and Canada Foundation for Innovation/Ontario Research Fund: 27881 (TJM). Salaries: Postdoctoral fellowships: Heart & Stroke/Richard Lewar Centre of Excellence (HP); graduate scholarships: University of Toronto (UofT) (AJ, NZ, TTT, RE), UofT Faculty of Dentistry Harron (RE), Queen Elizabeth II (TTT); undergraduate scholarships: CIHR Institute of Musculoskeletal Health and Arthritis (MA, MP, YZ), NSERC (TTT), UofT Faculty of Dentistry (MA), UofT Work Study (YRK, TTT, MA), and Ontario Summer Experience Program (YRK).