B cell function and influenza vaccine responses in healthy aging and disease

Frasca, Daniela; Blomberg, Bonnie B.

doi:10.1016/j.coi.2014.05.008

Cited by 56 publications

(43 citation statements)

References 72 publications

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“…We have previously established that by 60 years of age we see deficits in all of the markers we measure in B cells (reviewed in Refs. ). We enrolled nine individuals/group, after appropriate signed informed consent and IRB protocol #20070481 approval at the University of Miami.…”

Section: Methodsmentioning

confidence: 97%

Obesity decreases B cell responses in young and elderly individuals

Frasca

Ferracci

Diaz

et al. 2016

Obesity

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Objective To evaluate the effects of obesity-associated inflammation on influenza vaccine responses. Methods We measured in young and elderly individuals, both lean and with obesity, antibody responses to influenza vaccination. Results We found 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. In vitro B cell function was measured by activation-induced cytidine deaminase (AID) 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.

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Section: Methodsmentioning

confidence: 97%

Obesity decreases B cell responses in young and elderly individuals

Frasca

Ferracci

Diaz

et al. 2016

Obesity

Self Cite

191

203

View full text Add to dashboard Cite

show abstract

“…Aging substantially impacts the immune system (1), manifesting as declining or dysregulated immune responses, more severe complications from bacterial infections, reduced vaccine response, and dysfunction of B and T cells (2, 3). Disease resulting from infection constitutes one third of mortality in the global population aged 65 or older (4).…”

Section: Introductionmentioning

confidence: 99%

Aging-Impaired Filamentous Actin Polymerization Signaling Reduces Alveolar Macrophage Phagocytosis of Bacteria

Jiao

Fan

et al. 2017

The Journal of Immunology

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In elderly patients bacterial infection often causes severe complications and sepsis. Compared to younger patients, older patients are more susceptible to sepsis caused by respiratory infection. Macrophage (Mϕ) phagocytosis of bacteria plays a critical role in the clearance of pathogens and the initiation of immune responses. It has been suggested that Mϕ exhibit age related functional alterations, including reduced chemotaxis, phagocytosis, antibacterial defense, and ability to generate reactive oxygen species. However, the mechanisms behind these changes remain unclear. The current study aimed at determining changes in bacterial phagocytosis in aging alveolar Mϕ (AMϕ) and the underlying mechanisms. We show that bacteria initiate cytoskeleton remodeling in AMϕ through interaction with macrophage receptor with collagenous structure (MARCO), a bacterial scavenger receptor. This remodeling, in turn, promotes enhanced cell surface expression of MARCO and bacterial phagocytosis. We further demonstrate that Rac1-GTP mediates MARCO signaling and activates actin-related protein-2/3 (Arp2/3) complex, a filamentous actin (F-actin) nucleator, thereby inducing F-actin polymerization, filopodia formation, and increased cell surface expression of MARCO, all of which are essential for the execution of bacteria phagocytosis. However, AMϕ isolated from aging mice exhibit suppressed Rac1 mRNA and protein expression, which resulted in decreases in Rac1-GTP levels and Arp2/3 activation, and subsequent attenuation of F-actin polymerization, filopodia formation and cell surface expression of MARCO. As a result, bacterial phagocytosis in aging AMϕ is decreased. This study highlights a previously unidentified mechanism by which aging impairs Mϕ phagocytosis of bacteria. Targeting these pathways may improve outcomes of bacterial infection in elderly patients.

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“…B cells exhibit intrinsic alterations such as impaired immunoglobulin class switching with aging that impair antibody responses to vaccination (82). B cells produce alloreactive antibodies against the transplant, leading to acute and chronic rejection (83)(84)(85).…”

Section: R E V I E W S E R I E S : T R a N S P L A N Tat I O Nmentioning

confidence: 99%