Table 1 Neonatal factors mediating susceptibility towards disease and their consequences for neonatal and adult disease
| Â | Disease | Host | Mediating factors | Consequences | References |
|---|---|---|---|---|---|
Neonatal susceptibilty towards intestinal disease | Early-onset colitis | Human | IL10R deficiency on hematopoietic cells | Colitis | |
| Â | Necrotizing enterocolitis (NEC) | Human | TLR4 signaling in intestinal epithelial and endothelial cells | Necrosis of intestinal tissue | |
| Â | Immune-mediated diseases after C-section delivery | Human/mouse | Altered microbiota, absence of epithelial tolerance towards Irak1 mediated signaling, altered priming of the adaptive immune system (?) | Increased intestinal epithelial apoptosis after colonization with E. coli | |
| Â | Rotavirus | Human/mouse | Decreased TLR3 expression and IFN signaling | Increased pathology, diarrhea | |
| Â | Shigella spp. | Mouse | Decreased Paneth cell AMPs | Inflammatory lesions in jejunum | |
|  | Cryptosporidium parvum | Mouse | Decreased IL-12 and IFN-γ production | Diarrhea | |
| Â | Salmonella Typhimurium | Human/mouse | Low colonization resistance, low mucin expression, lower epithelial turnover, endotoxin tolerance of IECs (?) | Intestinal colonization, epithelial SCV formation, systemic translocation | |
| Â | Group B streptococci | Human | ? | Meningitis, sepsis | Â |
| Â | E. coli K1 | Human/mouse | Low colonization resistance, decreased TLR4 signaling, decreased G-CSF and IL-17 production | Meningitis, sepsis | |
| Â | EHEC | Human/mouse | ? | (bloody) Diarrhea | |
| Â | EPEC | Human/mouse | ? | Watery diarrhea | |
|  | Yersinia entercocolitica | Mouse | Increased CD4 numbers, increased IFN-γ and IL-17 production in mesenteric lymph nodes | Enhanced survival of the neonates | |
| Â | Clostridium difficile | Human | ? | Absence of disease | |
Consequences for adult disease in the intestine | Immune-mediated diseases after C-section delivery | human | Altered priming of the adaptive immune system | Celiac disease, asthma | |
| Â | Colitis | Mouse | Reduced microbial exposure, increased CXCL16 production | Enhanced TNBS-mediated colitis | |
| Â | Antigen-induced oral anaphylaxis | Mouse | Reduced microbial exposure, IL-4 and T cell-dependent IgE class switch | Enhanced susceptibility to food allergy | |
Neonatal susceptibilty towards pulmonary disease | Allergic inflammation | Mouse | Microbial exposure, absence of iTreg cells, intrinsic Th2 bias of CD4+ T cells | Increased Th2 inflammation, increased DC activation | |
|  | RSV infection | Mouse | Attenuated/delayed IFN-γ production, increased IL-13 production, low-avidity CD8 T-cell response with distinct epitope-specificity, RSV-specific IgE | No direct effect on primary infection, effect seen upon reinfection | |
Consequences for adult disease in the lungs | Reinfection with RSV | Mouse | Elevated production of inflammatory mediators during reinfection, enhanced inflammatory cell infiltration during reinfection, RSV-specific IgE upon primary infection, production of IL-13 during primary infection, low amounts of IFN-γ produced during primary infection | Increased weight loss/immunopathology, airway hyperresponsiveness, enhanced mucus production and airway eosinophilia | |
| Â | Adult asthma | Mouse/human | Aggravating factors: reduced microbial exposure (antibiotic treatment), RSV infection, maternal tobacco smoke exposure | Aggravating consequences: increased baseline serum IgE levels, reduced Treg cell numbers, alteration in microbial load/composition, Th2-bias of Tregs | |
| Â | Â | Â | Alleviating factors: breast feeding, farm exposure (maternal or neonatal) | Alleviating consequences: increased Treg cell numbers, alterations in microbial composition |
