Premium
Neonatal and aged mice are unable to respond to polysaccharide antigens due to an up regulation in p38 MAPK
Author(s) -
Chelvarajan Lakshman,
Popa Diana,
Hersh Matthew,
Getchell Thomas,
Stromberg Arnold,
Bondada Subbarao
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1070.27
Subject(s) - chemokine , p38 mitogen activated protein kinases , immune system , receptor , cytokine , chemistry , immunology , endocrinology , biology , medicine , mapk/erk pathway , microbiology and biotechnology , signal transduction
Due to the inability of the immune systems of aged and neonatal humans and rodents to make sufficient Ab to the capsular polysaccharides (PS), they are susceptible to infections by PS encapsulated bacteria. This lack of anti‐PS Ab is due to MΦ not being able to produce B cell stimulatory cytokines. When stimulated by TLR agonists, murine neonatal and aged MΦ make less pro‐inflammatory cytokines (p‐ic) and more IL‐10 than adult MΦ. Neutralization of IL‐10 allowed them to produce levels of p‐ic comparable to that produced by young adult MΦ. A microarray analysis was performed on RNA from resting and TLR‐4‐stimulated murine splenic MΦ. Expression of genes encoding the TLR signaling pathway, cytokines, chemokines, and their receptors was decreased in neonatal and aged MΦ, but p38 MAPK was enhanced in neonatal and aged MΦ. Surprisingly p38 had a dual role in p‐ic production with excess p38 levels being inhibitory. Suboptimal levels of p38 inhibitor enhanced p‐ic production but inhibited IL‐10 production. In vivo, a partial inhibition of p38 also suppressed TLR‐4 induced IL‐10 production without affecting p‐ic production. A partial inhibition of p38, considerably enhanced production of PS specific Ab in aged mice. TLR‐4 induced IL‐10 production was similarly dependent on p38 in human cord blood monocytes. Thus, elevated p38 activity in aged and neonatal MΦ leads to diminished help for B cells to mount an Ab response against PS.