title: A humoral immune defect distinguishes the response to Staphylococcus aureus infections in mice with obesity and type 2 diabetes from that in mice with type 1 diabetes.
abstract: Obesity and diabetes are among the greatest risk factors for infection following total joint arthroplasty. However, the underlying mechanism of susceptibility is unclear. We compared orthopedic implant-associated Staphylococcus aureus infections in type 1 (T1D) versus type 2 (T2D) diabetic mouse models and in patients with S. aureus infections, focusing on the adaptive immune response. Mice were fed a high-fat diet to initiate obesity and T2D. T1D was initiated with streptozotocin. Mice were then given a trans-tibial implant that was precoated with bioluminescent Xen36 S. aureus. Although both mouse models of diabetes demonstrated worse infection severity than controls, infection in T2D mice was more severe, as indicated by increases in bioluminescence, S. aureus CFU in tissue, and death within the first 7 days. Furthermore, T2D mice had an impaired humoral immune response at day 14 with reduced total IgG, decreased S. aureus-specific IgG, and increased IgM. These changes were not present in T1D mice. Similarly, T2D patients and obese nondiabetics with active S. aureus infections had a blunted IgG response to S. aureus. In conclusion, we report the first evidence of a humoral immune deficit, possibly due to an immunoglobulin class switch defect, in obesity and T2D during exacerbated S. aureus infection which may contribute to the increased infection risk following arthroplasty in patients with T2D and obesity.
authors: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors: Christopher W
authors: CW
authors: Farnsworth
authors: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors: Cindy T
authors: CT
authors: Shehatou
authors: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors: Robert
authors: R
authors: Maynard
authors: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors: Kohei
authors: K
authors: Nishitani
authors: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors: Stephen L
authors: http://orcid.org/0000-0003-0005-8694
authors: SL
authors: Kates
authors: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors: Michael J
authors: MJ
authors: Zuscik
authors: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors: Edward M
authors: EM
authors: Schwarz
authors: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors: John L
authors: JL
authors: Daiss
authors: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA Robert_Mooney@urmc.rochester.edu.
authors: Robert A
authors: RA
authors: Mooney
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D018149:Glucose Intolerance; D006801:Humans; D056724:Immunity, Humoral; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000276:immunology*; D010019:Osteomyelitis / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus