Exacerbated staphylococcus aureus foot infections in obese/diabetic mice are associated with impaired germinal center reactions, Ig class switching, and humoral immunity

Christopher W. Farnsworth, Eric M. Schott, Abigail Benvie, Stephen L. Kates, Edward M. Schwarz, Steven R. Gill, Michael J. Zuscik, Robert A. Mooney

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Obese patients with type 2 diabetes (T2D) are at an increased risk of foot infection, with impaired immune function believed to be a critical factor in the infectious process. In this study, we test the hypothesis that humoral immune defects contribute to exacerbated foot infection in a murine model of obesity/T2D. C57BL/6J mice were rendered obese and T2D by a high-fat diet for 3 mo and were compared with controls receiving a low-fat diet. Following injection of Staphylococcus aureus into the footpad, obese/T2D mice had greater foot swelling and reduced S. aureus clearance than controls. Obese/T2D mice also had impaired humoral immune responses as indicated by lower total IgG levels and lower anti–S. aureus Ab production. Within the draining popliteal lymph nodes of obese/T2D mice, germinal center formation was reduced, and the percentage of germinal center T and B cells was decreased by 40–50%. Activation of both T and B lymphocytes was similarly suppressed in obese/T2D mice. Impaired humoral immunity in obesity/T2D was independent of active S. aureus infection, as a similarly impaired humoral immune response was demonstrated when mice were administered an S. aureus digest. Isolated splenic B cells from obese/T2D mice activated normally but had markedly suppressed expression of Aicda, with diminished IgG and IgE responses. These results demonstrate impaired humoral immune responses in obesity/T2D, including B cell–specific defects in Ab production and class-switch recombination. Together, the defects in humoral immunity may contribute to the increased risk of foot infection in obese/T2D patients.

Original languageEnglish
Pages (from-to)560-572
Number of pages13
JournalJournal of Immunology
Volume201
Issue number2
DOIs
StatePublished - Jul 15 2018

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