the effects of milk proteins on immunity: mechanisms and implications rjj van neerven...

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