"Microbial Old Friends"      Graham Rook  

Does exposing infants to cleaning agents containing detergents and substances causing cell death (and release of dsDNA) predispose to allergic disorders?

There is much controversy over the role of cleaning agents in the increased prevalence of allergic disorders. We have discussed this issue here.

There is increasing evidence that damage to epithelial barriers can accelerate entry of potential allergens into the the tissues of the gut or airways. Moreover, if a toxic substance is also present there may be cell death leading to release of double stranded DNA (dsDNA) which acts as a "danger signal", and as a Th2 adjuvant. Normally antigens that enter the gut or airways drive tolerance. However as illustrated in the figure below, an allergen encountered in the presence of a danger signal may predispose the immune system to generate the type of immune response that evolved to drive immediate expulsion of the cell-damaging agent.

Then the next time the same allergen is encountered it acts a a proxy for the toxic substance which cannot elicit an immune response to itself because it is not an antigen (for example, bleach). This scenario is illustrated in the figure below. (Figure adapted from figure 2 in:- Rook & Bloomfield (2021) J Allergy Clin Immunol 148:33-9). The paper can be downloaded here.
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The pathway that recognises cytosolic dsDNA is illustrated in the figure below.

Interestingly, cGAS, the molecule that detects cytosolic dsDNA, appears to be essential for the development of airway allergy (also shown as ref 4 on the figure below, together with other references that support this hypothesis).
Therefore damage to epithelial barriers accompanied by cell death in the airways might cause infants to develop allergic responses to allergens that happen to be present at the same time as the exposure to bleach/detergent mixtures, or to other agents with similar properties.
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Exposure of infants to such cleaning agents is likely to occur in homes of low SES where the mother may be cleaning while looking after infants, whereas in wealthy homes the cleaning is done by cleaning personnel, and the infant will not usually be present.

We suggest that the infant airways are particularly susceptible to this effect, whereas exposure of adults to similar detergents and chemicals might elicit different patterns of response, such as those seen in professional cleaning personnel, exposed every day to these materials during their employment.

This hypothesis deserves detailed study. If correct it could lead to rather easy ways of reducing the burden of childhood allergy.