microflora and immunomodulation; asthma and allergy prevention; dendritic cell subsets; immune tolerance; bacterial immunomodulators; models of allergy and inflammatory disorders; inflammasome activation
Nicole Tegtmeyer, Steffen Backert (2017), Molecular Pathogenesis and Signal Transduction by Helicobacter pylori
, Springer, Schweiz.
Steffen Backert (2016), Inflammasome Signaling and Bacterial Infections
, Springer, Schweiz.
Mejías-Luque Raquel, Zöller Jessica, Anderl Florian, Loew-Gil Elena, Vieth Michael, Adler Thure, Engler Daniela B, Urban Sabine, Browning Jeffrey L, Müller Anne, Gerhard Markus, Heikenwalder Mathias (2016), Lymphotoxin β receptor signalling executes Helicobacter pylori-driven gastric inflammation in a T4SS-dependent manner., in Gut
Smits Hermelijn H, Hiemstra Pieter S, Prazeres da Costa Clarissa, Ege Markus, Edwards Michael, Garn Holger, Howarth Peter H, Jartti Tuomas, de Jong Esther C, Maizels Rick M, Marsland Ben J, McSorley Henry J, Müller Anne, Pfefferle Petra I, Savelkoul Huub, Schwarze Jürgen, Unger Wendy W J, von Mutius Erika, Yazdanbakhsh Maria, Taube Christian (2016), Microbes and asthma: Opportunities for intervention., in The Journal of allergy and clinical immunology
, 137(3), 690-7.
Kyburz Andreas, Müller Anne (2016), The Gastrointestinal Tract Microbiota and Allergic Diseases., in Digestive diseases (Basel, Switzerland)
, 34(3), 230-43.
Djekic Aleksandra, Müller Anne (2016), The Immunomodulator VacA Promotes Immune Tolerance and Persistent Helicobacter pylori Infection through Its Activities on T-Cells and Antigen-Presenting Cells., in Toxins
, 8(6), 1-10.
Hartung Mara L, Gruber Dorothea C, Koch Katrin N, Grüter Livia, Rehrauer Hubert, Tegtmeyer Nicole, Backert Steffen, Müller Anne (2015), H. pylori-Induced DNA Strand Breaks Are Introduced by Nucleotide Excision Repair Endonucleases and Promote NF-κB Target Gene Expression., in Cell reports
, 13(1), 70-9.
Koch Katrin N, Müller Anne (2015), Helicobacter pylori activates the TLR2/NLRP3/caspase-1/IL-18 axis to induce regulatory T-cells, establish persistent infection and promote tolerance to allergens., in Gut microbes
, 6(6), 382-7.
Engler Daniela B, Leonardi Irina, Hartung Mara L, Kyburz Andreas, Spath Sabine, Becher Burkhard, Rogler Gerhard, Müller Anne (2015), Helicobacter pylori-specific protection against inflammatory bowel disease requires the NLRP3 inflammasome and IL-18., in Inflammatory bowel diseases
, 21(4), 854-61.
Koch Katrin N, Hartung Mara L, Urban Sabine, Kyburz Andreas, Bahlmann Anna S, Lind Judith, Backert Steffen, Taube Christian, Müller Anne (2015), Helicobacter urease-induced activation of the TLR2/NLRP3/IL-18 axis protects against asthma., in The Journal of clinical investigation
, 125(8), 3297-302.
The gram-negative bacterial pathogen Helicobacter pylori is predominantly known for its tight association with peptic ulcer disease and gastric cancer. However, recent epidemiological evidence suggests that chronic infection with H. pylori may at the same time be beneficial to the host by conferring protection against asthma, other allergic disease manifestations and inflammatory bowel diseases (IBD). We have recently provided the first definitive experimental evidence showing that allergen-induced asthma fails to develop in H. pylori-infected mice. The protective effects are particularly evident in mice infected at an early age, and depend on the H. pylori-mediated induction of regulatory T-cells (Tregs) with highly suppressive activity. H. pylori infection efficiently reprograms dendritic cells in the stomach-draining lymph nodes towards a tolerance-promoting phenotype; the “tolerogenic” activity of H. pylori-experienced DCs requires DC-intrinsic inflammasome activation and secretion of interleukin-18. Interestingly, active tolerization with H. pylori extract is as efficient as live infection in preventing asthma. Within this grant, we will first explore the mechanistic basis of H. pylori-induced immune tolerance and will then exploit the immunomodulatory properties of the bacteria for the development of innovative new asthma and allergy prevention and treatment strategies.