A new twist to the hygiene hypothesis shows that allergic risk can also be modulated by microbial exposure before birth. Mice born to dams that were exposed to bacteria during pregnancy were less likely to develop allergic responses than those born to unexposed mothers. And maternal Toll-like receptor (TLR) signals were required for the transmission of protection.
TLRs are a type of pattern recognition receptor (PRR) and recognise molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs).
The progressive rise in allergies in the past several decades is often attributed to an increasing tendency to keep kids too clean or at least away from ‘old friends’ including certain bacteria, viruses and other parasites including worms —a theory known as the hygiene hypothesis. According to this theory, exposure of young children to environmental microbes conditions the developing immune system to tolerate microbes and allergens later in life.
Studies have shown, for example, that children raised on farms, where there is a far greater exposure to various microbes, developed fewer allergies than those raised in cities or non-farming rural regions. But it may not be the kids’ exposure that counts; children of farming mothers are also less susceptible to allergies regardless of their own exposure. But the biological mechanisms behind this phenomenon have been less clear.
According to the new study by Harald Renz and colleagues at the Phillips-University of Marburg, pregnant mice exposed to inhaled barnyard microbes gave birth to allergy-resistant pups.
The exposure triggered a mild inflammatory response in the mothers, characterised by the increased expression of microbe-sensing “Toll-like” receptors (TLRs) and the production of immune molecules called cytokines.
The maternal TLRs were essential for transmitting protection, but how TLR signals translate into allergy resistance in the offspring is not yet known. It also remains to be seen whether the protection applies to a broad range of allergens, including those found in food.
Holt PG, Strickland DH.Soothing signals: transplacental transmission of resistance to asthma and allergy. J Exp Med. 2009 Dec 7. View Full Article
Conrad ML, Ferstl R, Teich R, Brand S, Blümer N, Yildirim AO, Patrascan CC, Hanuszkiewicz A, Akira S, Wagner H, Holst O, von Mutius E, Pfefferle PI, Kirschning CJ, Garn H, Renz H. Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. J Exp Med. 2009 Dec 7. View Abstract