OBJECTIVE: To evaluate the effects of obesity-associated inflammation on influenza vaccine responses. METHODS: In young and elderly individuals, both lean and with obesity, antibody responses to influenza vaccination were measured. RESULTS: A decrease in in vivo vaccine responses, circulating switched memory, and transitional B cells and an increase in pro-inflammatory late/exhausted memory B cells were found. In vitro B cell function was measured by activation-induced cytidine deaminase and E47, markers of optimal antibody responses. Moreover, IL-6 production was increased, whereas IL-10 production was decreased in cultures of B cells from individuals with obesity. Markers of immune activation (TNF-α, TLR4, micro-RNAs) in unstimulated B cells were also found increased and were negatively correlated with B cell function. In order to reveal potential mechanisms, we stimulated B cells from lean individuals in vitro with leptin, the adipokine increased in obesity. Leptin increased phospho-STAT3, crucial for TNF-α production, and decreased phospho-AMPK, the energy sensing enzyme upstream of phospho-p38 MAPK and E47. Leptin-induced phospho-STAT3 and phospho-AMPK levels were similar to those in B cells from individuals with obesity. CONCLUSIONS: These results demonstrate that leptin can be responsible for decreased B cell function in obesity.
OBJECTIVE: To evaluate the effects of obesity-associated inflammation on influenza vaccine responses. METHODS: In young and elderly individuals, both lean and with obesity, antibody responses to influenza vaccination were measured. RESULTS: A decrease in in vivo vaccine responses, circulating switched memory, and transitional B cells and an increase in pro-inflammatory late/exhausted memory B cells were found. In vitro B cell function was measured by activation-induced cytidine deaminase and E47, markers of optimal antibody responses. Moreover, IL-6 production was increased, whereas IL-10 production was decreased in cultures of B cells from individuals with obesity. Markers of immune activation (TNF-α, TLR4, micro-RNAs) in unstimulated B cells were also found increased and were negatively correlated with B cell function. In order to reveal potential mechanisms, we stimulated B cells from lean individuals in vitro with leptin, the adipokine increased in obesity. Leptin increased phospho-STAT3, crucial for TNF-α production, and decreased phospho-AMPK, the energy sensing enzyme upstream of phospho-p38 MAPK and E47. Leptin-induced phospho-STAT3 and phospho-AMPK levels were similar to those in B cells from individuals with obesity. CONCLUSIONS: These results demonstrate that leptin can be responsible for decreased B cell function in obesity.
Authors: Daniela Frasca; Alain Diaz; Maria Romero; Mitch Phillips; Nicholas V Mendez; Ana Marie Landin; Bonnie B Blomberg Journal: Int Immunol Date: 2012-01-25 Impact factor: 4.823
Authors: Daniela Frasca; Maria Romero; Ana Marie Landin; Alain Diaz; Richard L Riley; Bonnie B Blomberg Journal: Mech Ageing Dev Date: 2010-02-26 Impact factor: 5.432
Authors: Daniela Frasca; Alain Diaz; Maria Romero; Nicholas V Mendez; Ana Marie Landin; Bonnie B Blomberg Journal: Immun Ageing Date: 2013-04-22 Impact factor: 6.400
Authors: Rasagna Kosaraju; William Guesdon; Miranda J Crouch; Heather L Teague; E Madison Sullivan; Erik A Karlsson; Stacey Schultz-Cherry; Kymberly Gowdy; Lance C Bridges; Lauren R Reese; P Darrell Neufer; Michael Armstrong; Nichole Reisdorph; J Justin Milner; Melinda Beck; Saame Raza Shaikh Journal: J Immunol Date: 2017-05-12 Impact factor: 5.422