Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens

R. L. Chelvarajan, S. M. Collins, I. E. Doubinskaia, S. Goes, J. Van Willigen, D. Flanagan, W. J.S. De Villiers, J. S. Bryson, S. Bondada

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


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 cytoldnes, 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 hi expression of Tool-like receptor-2 (TLR-2) and TLR-4 and CD14.

Original languageEnglish
Pages (from-to)982-994
Number of pages13
JournalJournal of Leukocyte Biology
Issue number6
StatePublished - Jun 2004


  • B lymphocytes
  • Cytokines
  • LPS
  • Suppression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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