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08 December 2009J. Exp. Med., edited by Infection Research
Allergy risk is modulated before birth
The risk of developing allergies is already modulated in the womb. According to studies in mice, prenatal exposure to farming-related microbes protects the offspring from developing allergic asthma. Functional maternal Toll-like receptor (TLR) signaling is essential for transmission of immunity from the mother to the fetus, scientists from Germany and Japan report in the Journal of Experimental Medicine.
Harald Renz of the Philipps-University of Marburg and colleagues exposed pregnant mice intranasally to Acinetobacter lwoffi, a bacterium commonly found in cowsheds. Offspring of these mice developed strong resistance to experimental asthma after sensitization and challenge with ovalbumin, the team reports.
Maternal exposure to A. lwoffi triggered a mild inflammatory response characterized by an increase in the production of proinflammatory cytokines in the lungs and serum and up-regulation of mRNA for various TLRs in lung tissue. Conversely, in placental tissue TLR production was down-regulated, the scientists further report.
In knockout mice lacking multiple TLRs (TLR 2, 3, 4, 7 and 9), the asthma-protective effect in the offspring was lost. These animals developed airway inflammation, goblet cell metaplasia and mucus production after challenge with ovalbumin.
A significant role for direct transfer of bacterial endotoxins to the fetus in antenatal programming was ruled out. The scientists tested other microbes with similar results.
"Our data provide strong evidence in favor of the hygiene hypothesis and demonstrate how prenatal asthma-protective effects from maternal microbial treatment are transferred from the mother to the progeny", Renz et al. write. "Collectively, the results of our study elucidate a novel mechanism for prenatal asthma protection and may incite novel clinical approaches for allergy and asthma prevention."
The results of the study are discussed in an accompanying commentary by Patrick Holt and Deborah Strickland (Telethon Institute for Child Health Research, University of Western Australia).
Study: Melanie Conrad, Ruth Ferstl, René Teich, Stephanie Brand, Nicole Blümer, Harald Renz et al.: Maternal TLR signalin is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. J. Exp. Med., doi: 10.1084/jem.20090845.
Comment: Patrick Holt and Deborah Strickland: Soothing signals: transplancental transmission of resistance to asthma and allergy. J. Exp. Med., doi: 10.1084/jem.20092469.
