Density of dendritic cells in the human tracheal mucosa is age dependent and site specific

Abstract

Background: The mucosal immune system undergoes extensive changes in early childhood in response to environmental stimuli. Dendritic cells (DC) play a major role in the development of the immune system. However, few data exist on the influence of continuous environmental stimulation on the distribution and phenotype of human airway DC. Methods: Human tissue samples are mostly paraffin embedded which limits the use of several antibodies, and respiratory tissue for cryopreservation is difficult to obtain. Human frozen post mortem tracheal tissue was therefore used for this study. Only samples with epithelial adherence to the basement membrane were included (n = 34). Immunohistochemical staining and sequential overlay immunofluorescence were performed with DC-SIGN and a panel of leucocyte markers co-expressed by DC. Results: DC detected in the human tracheal mucosa using DC-SIGN correlated with the expression of HLA-DR, co-stimulatory and adhesion molecules. Higher cell densities were found at the ventral tracheal site of patients older than 1 year than in infants in the first year of life. Conclusion: The increasing population of mucosal DC with age could reflect immunological maturation.

Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age

“…This finding suggested that the influx of APC into the airway mucosa is a very slow process during infancy. However, more recently the same group reported from SIDS cases that the tracheal mucosa contained a relatively high number of HLA-DR + cells, similar to that found here (200–300 cells/mm 2 of lamina propria) 26. The striking difference between their two studies might be explained by the fact that the first one was performed on formalin fixed and paraffin embedded tissue whereas the latter was performed on frozen sections.…”

“…However, the latter study by Tschernig and colleagues26 suggested that the density of APC found by us could in fact reflect the normal situation within this age group. Although respiratory infections have been suggested to contribute to the pathogenesis of SIDS, many studies have failed to document overt signs of mucosal inflammation in the victims 27 28.…”

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung

“…In support, the spontaneous wave of type 2 immunity around PND14 was intact in Rag2-deficient mice, and ILC2 accumulations were even enhanced in these mice, most likely due to increased availability of IL-2 in Rag2 À/À mice. Studies in neonatal rodents and humans reported scarcity as well as immaturity of pulmonary DCs, hyporesponsiveness to PAMPs, and low lymphocyte numbers and therefore suggested incompetence of the early postnatal pulmonary immune system to mount adaptive immune responses, an effect that was even exacerbated in germ-free mice (Belderbos et al, 2009;Gollwitzer et al, 2014;Nelson and Holt, 1995;Nelson et al, 1994;Roux et al, 2011;Tschernig et al, 2006). In accordance with these studies, we found that DCs were indeed severely impaired in neonatal lungs, and the few CD11b + DCs in neonatal lungs during the first post-natal week were sessile CD11b + CD64 + moDCs that closely resemble macrophages Plantinga et al, 2013).…”

Immunology of infants through adolescents: responses to emulate for HIV vaccines

“…Although cord blood dendritic cells, the principal antigen presentation cells of the body, seem to be immature [71], not much is known about human neonatal mucosal dendritic cells at the gut and respiratory tract [72]. The density of dendritic cells in the human trachea appears to be low in infants under 1 year of age [73]. In response to infection, however, dendritic cells may increase in frequency [74].…”