Mycobacterial infection aggravates Helicobacter pylori-induced gastric preneoplastic pathology by redirection of de novo induced Treg cells
Mariela Artola-Borán,
Angela Fallegger,
Martina Priola,
Rima Jeske,
Tim Waterboer,
Anders B. Dohlman,
Xiling Shen,
Sebastian Wild,
Jiazhuo He,
Mitchell P. Levesque,
Shida Yousefi,
Hans-Uwe Simon,
Phil F. Cheng,
Anne Müller
Affiliations
Mariela Artola-Borán
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
Angela Fallegger
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
Martina Priola
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
Rima Jeske
Infection and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
Tim Waterboer
Infection and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
Anders B. Dohlman
Department of Biomedical Engineering, Center for Genomics and Computational Biology, Duke Microbiome Center, Duke University, Durham, NC, USA
Xiling Shen
Department of Biomedical Engineering, Center for Genomics and Computational Biology, Duke Microbiome Center, Duke University, Durham, NC, USA
Sebastian Wild
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
Jiazhuo He
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
Mitchell P. Levesque
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
Shida Yousefi
Institute of Pharmacology, University of Bern, Bern, Switzerland
Hans-Uwe Simon
Institute of Pharmacology, University of Bern, Bern, Switzerland; Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia; Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia; Institute of Biochemistry, Medical School Brandenburg, Neuruppin, Germany
Phil F. Cheng
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
Anne Müller
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland; Corresponding author
Summary: The two human pathogens Helicobacter pylori and Mycobacterium tuberculosis (Mtb) co-exist in many geographical areas of the world. Here, using a co-infection model of H. pylori and the Mtb relative M. bovis bacillus Calmette-Guérin (BCG), we show that both bacteria affect the colonization and immune control of the respective other pathogen. Co-occurring M. bovis boosts gastric Th1 responses and H. pylori control and aggravates gastric immunopathology. H. pylori in the stomach compromises immune control of M. bovis in the liver and spleen. Prior antibiotic H. pylori eradication or M. bovis-specific immunization reverses the effects of H. pylori. Mechanistically, the mutual effects can be attributed to the redirection of regulatory T cells (Treg cells) to sites of M. bovis infection. Reversal of Treg cell redirection by CXCR3 blockade restores M. bovis control. In conclusion, the simultaneous presence of both pathogens exacerbates the problems associated with each individual infection alone and should possibly be factored into treatment decisions.
