The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9−/− knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78–treated TLR2/3/4/7/9−/− homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78–exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.
Papain is a proteolytic enzyme widely used by biochemists. In experiments on animals papain has been shown to cause emphysema either when they inhaled a single small dose or after intratracheal inhalation. Four food technologists were occupationally exposed to heavy concentrations of papain dust in air. Subjects 1 and 2 developed an immediate acute asthmatic reaction, and symptoms of obstructive airways disease persisted for some months while each remained in the same working area, presumably exposed to small gradually diminishing amounts of residual papain dust. Tests of respiratory function were carried out on all four subjects 1 1/2 years later and showed in subjects 1 and 3 minimal abnormality of bronchial reactivity and of ventilation distribution. Review of the literature reveals only two reports of asthma resulting from papain inhalation, although its antigenic and skin sensitizing qualities have been known and described for many years. It seems remarkable that a substance such as papain, shown to be a potent cause of lung damage in experimental animals, should have produced so little evidence of abnormality in our subjects after considerable exposure. Follow-up ventilatory function tests may cast further light on this but we postulate that the asthmatic response may be biologically protective and those lacking this reaction could later develop emphysema as a long-term outcome.
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