the effects of milk proteins on immunity: mechanisms and implications rjj van neerven...
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The effects of milk proteins on immunity: Mechanisms and implications
RJJ van Neerven
FrieslandCampina Research, Wageningen, The Netherlands
Cellbiology and Immunology Group, Wageningen University, Wageningen, the Netherlands
Milk is a natural, complete food full of functional components
It has two main functions:
• promoting development & growth
• and protection against infections
Paul Ehrlich: Transfer of immunity by milk
Maternal immunization of animals and subsequent breastfeeding protected
suckling mice against the toxins abrin and ricin (1892)
Transfer of immunity by milk
Paul Ehrlich (1854-1915)
Quote from : Kauffmann
Nature Immunol 2008
Transfer of immunity by milk: factors involved
Verhasselt, MucosalImmunology 2010
Most of these factors are also
present in cow’s milk !
Effects of farming on allergy development:Evidence from multiple epidemiological
studies
• Effect on asthma, rhinitis and wheezing
• Effect of stable and animal exposure
• Effect of milk consumption
• Effect of heating of raw milk
Protective effect of exposure to milk and stables
on development of allergy
Riedler et alLancet 2001
Epidemiological studies on the effect of farm milk consumption on allergies
Adapted from von Mutius and Vercelli
Nat. Rev. Immunol 2011
Heating status and milk protein levels are linked to the protective effect of farm milk on asthma
Loss et al J Allergy Clin Immunol, 2011
Raw milk consumption is associated with fewer upper airway infections in early life -1
Pasture study: A prospective birth cohort of 1100 children in 5 countries
* Statistically significant
Loss et alJACI in press
Reference group for milk types is UHT Shop milk.
Raw milk consumption is associated with fewer upper airway infections in early life -2
Pasture study: A prospective birth cohort of 1100 children in 5 countries
Loss et alJACI in press
Reference group for milk types is UHT Shop milk.
* Statistically significant
Binding of bovine IgG to human airway pathogens
Specificity of bovine immunoglobulins:Agglutination of pathogenic bacteria
Human serum IgG (IV Ig) and bovine milk IgG (bIg) bind to human RSV and influenza
Den Hartog et alSubmitted
IV IgbIg
Bovine IgG can prevent in vitro infection of human cells by human RSV
Concentration Ig (log(ug/ml))-4 -2 0 2 4
Inh
ibit
ion
RSV
(%
) 150
100
50
0
-50
Den Hartog et alSubmitted
Inhibition of HEp-2 infection by RSV-GFP
-4 -2 0 2 4-50
0
50
100
150SynagisIVIgboIg
Concentration (log (ug/ml))
Inh
ibit
ion
(%
)
Therapeutic Ab
Human serum Ig
Bovine milk Ig
Functions of immunoglobulins
Binding to bacteria, viruses and allergens
• Igs neutralise pathogens• Igs induce phagocytosis and killing of pathogens• Igs induce and enhance immune responses
+
Bovine IgG promotes phagocytosis of pathogens by human MoDC
Den Hartog et alSubmitted
How can raw milk consumption protect against respiratory infection and allergy ?
Adapted from van Neerven et al
JACI 2012
RSV infections are linked to otitis and asthma
Acknowledgements
WUR CBI:Huub SavelkoulGerco den Hartog
FrieslandCampinaLaurien UlfmanAnouk FeitsmaElise van de Weg-SchrijverTalitha EshuisAndre GroeneveldMargrethe JonkmanRolf Bos
UMCU/WKZJeanette LeusenGerco den Hartog
University MunichErika von MutiusGeorg LossMarcus Ege
WUR HMINico TaverneJerry Wells