Premium
Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens
Author(s) -
Chelvarajan R. L.,
Collins S. M.,
Doubinskaia I. E.,
Goes S.,
Van Willigen J.,
Flanagan D.,
Villiers W. J. S.,
Bryson J. S.,
Bondada S.
Publication year - 2004
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.0403179
Subject(s) - lipopolysaccharide , secretion , biology , cd14 , tumor necrosis factor alpha , macrophage , cytokine , immunology , antigen , interleukin , neonatal sepsis , interleukin 10 , antibody , receptor , immune system , medicine , endocrinology , sepsis , in vitro , biochemistry
Neonates do not respond to thymus‐independent (TI) antigens (Ag), making them vulnerable to infection with encapsulated bacteria. The antibody (Ab) response of adult and neonatal B cells to TI Ag requires certain cytokines, which are provided by T cells or macrophages (MΦ). Lipopolysaccharide (LPS) failed to induce neonatal MΦ to produce interleukin (IL)‐1β and tumor necrosis factor α (TNF‐α) mRNA and to secrete IL‐1β, IL‐12, and TNF‐α. However, LPS induced neonates to secrete some IL‐6 and three‐ to fivefold more IL‐10 than adults. Accordingly, adding adult but not neonatal MΦ could restore the response of purified adult B cells to trinitrophenol (TNP)–LPS, a TI Ag. Increased IL‐10 is causally related to decreased IL‐1β and IL‐6 production, as IL‐10 −/− neonatal MΦ responded to LPS by secreting more IL‐1β and IL‐6 than wild‐type (WT) neonatal MΦ. When cultures were supplemented with a neutralizing Ab to IL‐10, WT neonatal MΦ secreted increased amounts of IL‐6 and allowed neonatal MΦ to promote adult B cells to mount an Ab response against TNP–LPS. Thus, neonates do not respond to TI Ag as a result of the inability of neonatal MΦ to secrete cytokines, such as IL‐1β and IL‐6, probably as a result of an excess production of IL‐10. This dysregulated cytokine secretion by neonatal MΦ may be a result of a reduction in expression of Toll‐like receptor‐2 (TLR‐2) and TLR‐4 and CD14.