Differential maturation of the innate immune response in human fetuses.
Newborns and especially preterm infants show a unique susceptibility to severe bacterial infections that cause significant morbidity and mortality. As very few data are available on innate immune functions in human fetuses, we conducted a comprehensive study to investigate the expression of several adhesion molecules essentially involved in migration (CD11a, CD11b, CD11c, CD18, and CD62L). Furthermore, phagocytic activity, generation of respiratory burst products, and production of several proinflammatory cytokines were assessed. Various functions of the fetal innate immune system were demonstrated to be essentially different from those observed in term neonates or adults. Expression of several surface markers was significantly diminished on fetal granulocytes. Furthermore, a significantly reduced phagocytic activity of fetal granulocytes and monocytes was found, contrasted by an enhanced generation of reactive oxygen products. In addition, we demonstrate that significant numbers of fetal monocytes are capable of the production of proinflammatory cytokines in response to stimulation. However, the pattern of cytokine production is different from the more mature individuals: the number of IL-6- and tumor necrosis factor-alpha-positive monocytes were significantly diminished, whereas more IL-8-producing monocytes were found compared with adults. The results of our study add significantly to our understanding of the maturation and impairment of the innate immune response.
Strunk
Tobias
T
Department of Pediatrics, University of Lübeck, Medical School, Ratzeburger Allee 160, 23538 Lübeck, Germany. strunk@paedia.ukl.mu-luebeck.de
Temming
Petra
P
Gembruch
Ulrich
U
Reiss
Irwin
I
Bucsky
Peter
P
Schultz
Christian
C
D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D007223:Infant; D007231:Infant, Newborn; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis / Q000502:physiology; D011247:Pregnancy; D016897:Respiratory Burst
D015703:Antigens, CD; D016207:Cytokines