Helicobacter hepaticus infection in BALB/c mice abolishes subunit-vaccine-induced protection against M. tuberculosis.
BCG, the only licensed vaccine against tuberculosis (TB), provides geographically variable protection, an effect ascribed to exposure to environmental mycobacteria (EM). Here we show that altering the intestinal microbiota of mice by early-life infection with the commensal bacterium Helicobacter hepaticus (Hh) increases their susceptibility to challenge with Mycobacterium tuberculosis (Mtb). Furthermore Hh-infected mice immunised parenterally with the recombinant subunit vaccine, human adenovirus type 5 expressing the immunodominant antigen 85A of Mtb (Ad85A), display a reduced lung immune response and protection against Mtb challenge is also reduced. Expression of interleukin 10 (IL10) messenger RNA is increased in the colon of Hh infected mice. Treatment of Hh-infected Ad85A-immunised mice with anti-IL10 receptor antibody, following challenge with Mtb, restores the protective effect of the vaccine. These data show for the first time that alteration of the intestinal microbiota by addition of a single commensal organism can profoundly influence protection induced by a TB subunit vaccine via an IL10-dependent mechanism, a result with implications for the deployment of such vaccines in the field.
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Roosevelt Drive, Oxford, UK.
Isabelle C
IC
Arnold
The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, UK.
Claire
C
Hutchings
Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Ivanela
I
Kondova
The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, UK.
Ariann
A
Hey
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Roosevelt Drive, Oxford, UK.
Fiona
F
Powrie
The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, UK.
Peter
P
Beverley
The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, UK. Electronic address: elma.tchilian@pirbright.ac.uk.
Elma
E
Tchilian
D000260:Adenoviruses, Human / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D058491:Bacterial Load; D003106:Colon / Q000276:immunology; D000069196:Gastrointestinal Microbiome; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D044923:Helicobacter hepaticus / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D016753:Interleukin-10
Interleukin 10; Microbiota; Subunit vaccine; Tuberculosis