Abstracts (complete list) - Wissenschaft Online

Jennifer Debarry, Anna Hanuszkiewicz, Otto Holst, Holger Heine
Molecular mechanisms of human dendritic cell stimulation by
the Allergy-protective Lactococcus lactis strain G121
Exposure to farming environment during early childhood strongly influences the
development of allergic reactions later in life (“hygiene hypothesis”). As the first year of
life is important for the establishment of the THelper cell balance, environmental
influences such as increased exposure to certain bacteria might play a pivotal role in
adjusting this balance by promoting TH1 responses and thereby inhibiting TH2 responses
which are associated with allergies and asthma. The Gram-positive bacterium
Lactococcus lactis strain G121 was isolated from a cowshed and could be shown to
reduce allergic reactions in a mouse allergy model. Furthermore, we were able to show
a TH1 polarizing effect of L. lactis G121 in human dendritic cells (DCs) which might be
the underlying mechanism of the allergy-protective properties. Activation of DCs is
mainly mediated through NOD2 and the TH1 polarization by L. lactis G121 is impaired
after blocking the access to intracellular receptors via inhibition of phagocytosis. With
respect to the involved signal transduction pathways we next analyzed the NF-κB
pathway. In contrast to stimulation with E. coli we were unable to detect any substantial
translocation of p65 into the nucleus, even when the cells were monitored for up to 3
hrs. However, translocation of the c-Rel subunit into the nucleus was strongly
detectable within 120 min of stimulation. C-Rel is essential for the induction of TH1 polarizing cytokines since it controls IL12p35 and IL23p19 gene expression. In addition,
we detected a sustained activation of DCs for up to 48 hrs with respect to the TH1 polarizing IL12p35 and IL12p40 gene expression. This could be an important
mechanism for a prolonged triggering of an anti-allergic immune response (supported
by DFG, SFB/TR22, project A2).