Macrophages and Dendritic Cells

The crucial role of professional APC in initiating immune responses against pathogens and not towards self has recently been given much attention (Janeway Jr. 1992; Matzinger 1994; Wright 1999). Surprisingly little, however, is known about the neonatal macrophage and DC. The only monocyte/mf populations that have been functionally assessed come from umbilical cord blood samples collected at birth (Holt and Jones 2000). Neonatal macrophages have been reported to have reduced chemotaxis compared to adult levels (Baron and Lafuro 1985; Miller 1978; Speer and Johnson Jr. 1984; West 2002; Weston et al. 1997) and a decreased production of a number of cytokines, including TNF-a (Serushago et al. 1996). Several reports indicate that antigen processing impairments in neonatal mf lead to defective phagocytosis (Baron and Lafuro 1985; Holladay and Smialowicz 2000; West 2002), while several other reports suggest that these cells can phagocytose (Clerici et al. 1993) and present antigen at adult levels (Weston et al. 1997). Bactericidal activity in neonatal macrophages, however, have been reported to be at adult levels (Miller 1978; Speer and Johnson Jr. 1984).

A key to the concept of neonatal immunodeficiency may be the hindered ability of APC to produce IL-12 (Prescott et al. 2003). Specifically, DC derived from neonatal monocytes appear deficient in IL-12(p35) gene expression (Goriely et al. 2001). Addition of IFNg to the activated newborn DC restored expression of IL-12(p35) to adult levels, but because IL-12 is required for stabilization of the IFNg transcriptional machinery in T cells (Yap et al. 2000), a positive feedback loop seems to be curtailed (Goriely et al. 2001). In addition, neonatal DC have poor accessory function (Hunt et al. 1994) and express lower levels of ICAM-1 and MHC class I and II than peripheral blood DC from adults (reviewed in: Holt and Jones 2000). These characteristics further contribute to a decreased ability by neonatal DC to stimulate an adaptive immune response.

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