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

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.