The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function
Open Access
- 3 January 2005
- journal article
- pathophysiology
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 77 (4), 503-512
- https://doi.org/10.1189/jlb.0804449
Abstract
A reduction in macrophage (MΦ) function with aging makes mice less responsive to bacterial capsular polysaccharides, such as those present in the pneumococcal polysaccharide vaccine, a model of thymus independent (TI) antigen (Ag). Using trinitrophenol (TNP)-lipopolysaccharide (LPS) and TNP-Ficoll, two other well-studied TI Ag, we studied the mechanistic basis of reduced MΦ function in the aged. We show that aged mice are profoundly hyporesponsive to these TI Ag. As a result of a requirement for MΦ, highly purified B cells from young-adult mice do not respond to TI Ag. When purified, young B cells were immunized with TNP-Ficoll, the antibody production from those cultures reconstituted with MΦ from aged mice was significantly lower than that seen with young MΦ. Consequently, this unresponsiveness can be overcome by a mixture of interleukin (IL)-1β and IL-6. Upon stimulation with LPS, in comparison with young MΦ, aged MΦ secreted reduced amounts of IL-6, tumor necrosis factor α, IL-1β, and IL-12, cytokines necessary for B cells to respond to TI Ag. LPS also induced aged MΦ to produce an excess of IL-10. Neutralization of IL-10 enhanced the production of proinflamatory cytokines by MΦ upon LPS stimulation and also induced Ab production by aged splenocytes. Thus, the inability of aged MΦ to help the B cell response appears to be caused by an excess of IL-10. As aged MΦ have a reduced number of cells expressing Toll-like receptor 4 and CD14, the imbalance in cytokine production might be partly a result of fewer cells expressing key components of the LPS receptor complex.Keywords
Funding Information
- National Institutes of Health (AG05731, AI21490)
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