Hygiene Hypothesis

Hygiene Hypothesis: Are higher living standards and hygienic conditions responsible for an increasing prevalence of allergies?
I knew there was a reason I ate mudpies (as a kid)! I’ve even heard this connection thrown out in conversations between friends outside the field of science, and often wondered about the explanation according to immunology. As many of us may know, immunology is a literature base where few of us travel, unless necessary. But this feels like the perfect time to finally check it out.

The ‘hygiene hypothesis’ was first proposed by Strachan in 1989 to explain the relationship between modern healthcare and living practices that have reduced exposure to bacterial, viral or fungal components and increased risk for developing allergic disease. In his proposal, Strachan states that without the presence of these potentially allergy-preventing microbes, the immune system becomes imbalanced and this leads to predisposition to allergies.

Now, without the aid of our future lectures on T-cells and allergies, I will try to explain the details of this hypothesis. The major player of the adaptive immune cells in the initiation and perpetuation of allergies is the Th2 cell (T-helper cell type 2). Th2 cells contribute to the allergic immune response through release of cytokines IL4, IL5, IL9 and IL13 which promote three of the characteristic mechanisms of allergy. These include the shift toward IgE immunoglobulin production, the activity of eosinophils (proliferation, differentiation, recruitment and survival), and mucus production in the airways or gut. Th1 cells (T-helper cell type 1) can abrogate Th2 development and activity by producing the cytokine IFN-gamma. Tregs (regulatory T-cells) can also suppress Th2 activation. Romagnani et al. (2004) suggest that increased Th2 activities (specifically allergic immune responses) result from a decrease in the suppressive activities of Th1 and Treg cells.

Further, dendritic cells of the innate immune response aid in activating T-cells, and have also been implicated in the initiation and perpetuation of allergic immune responses. The types and activation status of the dendritic cell/antigen-presenting cell determines the type of T-cell response. For example, antigens presented in the presence of IL12 lead to Th1 development while antigens presented in the presence of IL4 lead to a Th2 response. Of note, dendritic cells that express surface marker CD11 have been shown as necessary and sufficient for induction of a Th2-driven allergic response. Also relevant to the hygiene hypothesis is that stimulation of antigen-presenting cells through Toll-like receptors (TLRs) leads mostly to induction of a Th1-driven immune response. Remember TLRs bind to pathogen-associated molecular patterns (PAMPs) that are characteristic of bacteria, viruses and fungi. These are the microbes that are missing in our highly hygienic modern environment. So the idea is that exposure at young ages (even in utero) to these microbes primes or activates the immune system in a way (Th1-driven) that prevents allergic sensitization (Th2-driven) later in life.

There are numerous animal studies that have shown this exact phenomena, that exposure to specific microbes (single bacterial strains like Mycobacterium bovis, whole cell vaccines like Bordetella pertussis, and LPS from bacteria, yeast and mycoplasma) exerts allergy-protective effects. Plus several very interesting connections between decreased microbe exposure and increased allergy production have been shown in human data studies (epidemiology). I was more interested in describing the immunologic mechanism for the hygiene hypothesis in this blog entry. However, I suggest reading the terrific review from Garn and Renz (2007), entitled “Epidemiological and immunological evidence for the hygiene hypothesis” for more engaging details.