Specific dietary oligosaccharides increase Th1 responses in a mouse respiratory syncytial virus infection model.
Breast feeding reduces the risk of developing severe respiratory syncytial virus (RSV) infections in infants. In addition to maternal antibodies, other immune-modulating factors in human milk contribute to this protection. Specific dietary prebiotic oligosaccharides, similar to oligosaccharides present in human milk, were evaluated in a C57BL/6 mouse RSV infection model. During primary RSV infection, increased numbers of RSV-specific CD4(+) T cells producing gamma interferon (IFN-γ) were found in the lungs at days 8 to 10 postinfection in mice receiving diet containing short-chain galactooligosacharides, long-chain fructooligosaccharides, and pectin-derived acidic oligosaccharides (termed scGOS/lcFOS/pAOS). In a Th2-skewed formalin-inactivated (FI)-RSV vaccination model, the prebiotic diet reduced RSV-specific Th2 cytokine (interleukin-4 [IL-4], IL-5, and IL-13)-producing CD4(+) T cells in the lung and the magnitude of airway eosinophilia at day 4 and 6 after infection. This was accompanied by a decreased influx of inflammatory dendritic cells (CD11b(+)/CD11c(+)) and increased numbers of IFN-γ-producing CD4(+) and CD8(+) T cells at day 8 after viral challenge. These findings suggest that specific dietary oligosaccharides can influence trafficking and/or effector functions of innate immune, CD4(+), and CD8(+) T cell subsets in the lungs of RSV-infected mice. In our models, scGOS/lcFOS/pAOS had no effect on weight but increased viral clearance in FI-RSV-vaccinated mice 8 days after infection. The increased systemic Th1 responses potentiated by scGOS/lcFOS/pAOS might contribute to an accelerated Th1/Th2 shift of the neonatal immune system, which might favor protective immunity against viral infections with a high attack rate in early infancy, such as RSV.
Department of Pediatrics, The Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
Marcel A
MA
Schijf
Debby
D
Kruijsen
Jacqueline
J
Bastiaans
Frank E J
FE
Coenjaerts
Johan
J
Garssen
Grada M
GM
van Bleek
Belinda
B
van't Land
D000818:Animals; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000276:immunology; D004032:Diet / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000008:administration & dosage*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology*
D022482:Cytomegalovirus Vaccines; D007155:Immunologic Factors; D009844:Oligosaccharides; D007371:Interferon-gamma