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The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function
Author(s) -
Chelvarajan R. Lakshman,
Collins Sarah M.,
Van Willigen Juliana M.,
Bondada Subbarao
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0804449
Subject(s) - biology , macrophage , function (biology) , polysaccharide , immunology , antigen , microbiology and biotechnology , biochemistry , in vitro
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.