Altered activation of neonatal alveolar macrophages affects the immune response to Pneumocystis.

Abstract Postnatal lung development renders a different lung environment and composition in neonates as compared to adults, making the neonatal immune response to lung pathogens, such as Pneumocystis (PC), less efficient than adults. Alveolar macrophages (AMs) are the major effector cells in the immune response to PC, and a proper AM activation phenotype is imperative for clearance of infection. Following peak infection, alternative markers (arginase, mannose receptor and CD23) are increased on adult AMs, suggesting a role for this phenotype in PC resolution. A more robust increase in these alternative markers is observed in neonates following peak infection. Additionally, naïve neonatal AMs constitutively express FIZZ1 and Ym1 at levels comparable to infected counterparts. It is possible that adult AMs develop a classical phenotype in the initial response to PC, and that this phenotype cannot be obtained by neonatal AMs early in infection due to increased expression of alternative markers. Additionally, increases in these alternative markers on neonatal AMs late in infection may suppress an efficient response to PC, thus resulting in delayed clearance as compared to adults. We hypothesize that delayed AM activation and increased expression of alternative markers during resolution results in an insufficient immune response to PC infection in neonates.