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Infection and Immunity, December 2002, p. 6688-6696, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6688-6696.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Innate Immune Responses of Human Neonatal Cells to Bacteria from the Normal Gastrointestinal Flora

Helen Karlsson,1 Christina Hessle,2 and Anna Rudin1*

Department of Rheumatology and Inflammation Research,1 Department of Clinical Bacteriology, Göteborg University, Göteborg, Sweden2

Received 5 July 2002/ Returned for modification 13 August 2002/ Accepted 12 September 2002

The hygiene hypothesis postulates that the prevalence of allergy has increased due to decreased microbial stimulation early in life, leading to delayed maturation of the immune system. The aim of this study was to examine the cytokine pattern produced from cord blood mononuclear cells relative to adult cells after stimulation with bacterial strains from the normal flora. Mononuclear cells from cord and adult blood samples were stimulated with the following bacteria: Bifidobacterium adolescentis, Enterococcus faecalis, Lactobacillus plantarum, Streptococcus mitis, Corynebacterium minutissimum, Clostridium perfringens, Bacteroides vulgatus, Escherichia coli, Pseudomonas aeruginosa, Veillonella parvula, and Neisseria sicca. The levels of interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-{alpha}), IL-10, and IL-6 were measured by enzyme-linked immunosorbent assay. The TNF-{alpha} production was also analyzed after blocking CD14, Toll-like receptor 2 (TLR-2), and TLR-4 prior to stimulation with bacteria. The levels of IL-12 and TNF-{alpha} were similar in cord and adult cells. Gram-positive bacteria induced considerably higher levels of IL-12 and TNF-{alpha} than gram-negative bacteria in both cord and adult cells. The levels of IL-6 were significantly higher in newborns than in adults, whereas the levels of IL-10 were similar in newborns and adults. Gram-negative and gram-positive bacteria induced similar levels of IL-6 and IL-10 in cord cells. L. plantarum bound or signaled through CD14, TLR-2, and TLR-4, whereas E. coli acted mainly through CD14 and TLR-4. These results indicate that the innate immune response in newborns to commensal bacteria is strong and also suggest that different bacterial strains may have differential effects on the maturation of the immune system of infants.

* Corresponding author. Mailing address: Department of of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10, 413 46 Göteborg, Sweden. Phone: 46-31-342 46 43. Fax: 46-31-82 39 25. E-mail: anna.rudin{at}microbio.gu.se.

Editor: J. D. Clements

Infection and Immunity, December 2002, p. 6688-6696, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6688-6696.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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