Neutrophil killing of Staphylococcus aureus in diabetes, obesity and metabolic syndrome: a prospective cellular surveillance study

被引:12
作者
Scully, Ingrid Lea [1 ]
McNeil, Lisa Kristin [1 ]
Pathirana, Sudam [1 ]
Singer, Christine Lee [1 ]
Liu, Yongdong [1 ]
Mullen, Stanley [1 ]
Girgenti, Douglas [1 ]
Gurtman, Alejandra [1 ]
Pride, Michael W. [1 ]
Jansen, Kathrin Ute [1 ]
Huang, Paul L. [2 ,3 ,4 ]
Anderson, Annaliesa S. [1 ]
机构
[1] Pfizer Vaccine Res & Dev, 401 North Middletown Rd, Pearl River, NY 10965 USA
[2] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA
[4] Harvard Med Sch, Boston, MA USA
关键词
Diabetes; Immune function; Metabolic syndrome; Neutrophils; Obesity; Staphylococcus aureus; Vaccine; VACCINE; INFECTIONS; IMMUNOGENICITY; INFLAMMATION; 4-ANTIGEN; SAFETY; PHASE; TOLERABILITY; MACROPHAGES; CAPACITY;
D O I
10.1186/s13098-017-0276-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Obesity, metabolic syndrome (MetS), and diabetes are frequent in surgical populations and can enhance susceptibility to postoperative surgical site infections. Reduced neutrophil function has been linked with diabetes and risk of Staphylococcus aureus infection. Therefore, neutrophil function in diabetic and obese subjects (+/- MetS) was assessed in this prospective serological and cellular surveillance study to determine whether vaccines administered to protect against infections after surgery could be effective in these populations. Methods: Neutrophil function (chemotaxis, phagocytosis, and opsonophagocytic killing of S. aureus) was assessed in subjects classified according to diabetes status, body mass index, and presence/absence of MetS. Neutrophils were characterized within functional subsets by flow cytometry. A serologic assay was used to measure baseline antibody presence to each antigen in SA4Ag: capsular polysaccharide (CP) type 5, CP8, recombinant mutant Clumping factor A (rmClfA), and recombinant Manganese transport protein C (rMntC). Results: Neutrophil function was similar for comorbid and healthy cohorts, with no significant between-group differences in cell counts, migration, phagocytosis ability, neutrophil subset proportions, and S. aureus killing ability when neutrophils were isolated 3-6 months apart (Visit 1 [n = 90] and Visit 2 [n = 70]) and assessed. Median pre-existing antibody titers to CP5, CP8, and rmClfA were comparable for all cohorts (insufficient subjects with rMntC titers for determination). Conclusions: MetS, diabetes, and obesity do not impact in vitro neutrophil function with regard to S. aureus killing, suggesting that if an effective S. aureus vaccine is developed it may be effective in individuals with these comorbidities.
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页数:13
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