title: Intracellular survival of Staphylococcus aureus in adipocyte-like differentiated 3T3-L1 cells is glucose dependent and alters cytokine, chemokine, and adipokine secretion.
abstract: Although obesity and type 2 diabetes mellitus are associated with Gram-positive infections and a worse clinical outcome, it is unknown whether adipocytes can be infected by Gram-positive bacteria. Adipocyte-like differentiated 3T3-L1 cells and Staphylococcus aureus were used for infection experiments under normoglycemic (100 mg/dl) and hyperglycemic (450 mg/dl) conditions in the presence/absence of insulin (1 μm). Intracellular presence and survival of S. aureus was investigated quantitatively. Supernatant cytokines, chemokines, and adipokines were measured by ELISA. Lipid metabolism and cellular morphology of infected adipocytes were investigated by different techniques. The present study provides the proof of principle that adipocyte-like cells can be infected by S. aureus dose dependently for up to 5 d. Importantly, low bacterial inocula did not affect cell viability. Intracellular survival of S. aureus was glucose dependent but not insulin dependent, and insulin receptor expression and insulin receptor signaling were not altered. Infection increased macrophage chemoattractant protein-1, visfatin, and IL-6 secretion, whereas resistin and adiponectin were decreased. Infected adipocytes had higher intracellular triacylglycerol concentrations and larger lipid droplets because of a decreased lipolysis. Taken together, infection of adipocytes by S. aureus is glucose dependent, inhibits cellular lipolysis, and affects the secretion of immunomodulating adipokines differentially. Because cell viability is not affected during infection, adipose tissue might function as a host for chronic infection by bacteria-causing metabolic, proinflammatory, and prodiabetic disturbances.
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93042 Regensburg, Germany. frank.hanses@klinik.uni-regensburg.de
authors.forename: Frank
authors.initials: F
authors.lastname: Hanses
authors.forename: Andrea
authors.initials: A
authors.lastname: Kopp
authors.forename: Margarita
authors.initials: M
authors.lastname: Bala
authors.forename: Christa
authors.initials: C
authors.lastname: Buechler
authors.forename: Werner
authors.initials: W
authors.lastname: Falk
authors.forename: Bernd
authors.initials: B
authors.lastname: Salzberger
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäffler
mesh_terms: D041721:3T3-L1 Cells / Q000378:metabolism / Q000382:microbiology*; D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D054392:Adipokines; D018925:Chemokines; D016207:Cytokines; D007328:Insulin; D005947:Glucose