The natural pre-colonization of the mouse digestive track by Helicobacter hepaticus and the modification of the intestinal microbiota appear to prevent the immune system from effectively controlling infection by Mycobacterium tuberculosis, the bacterium responsible for pulmonary tuberculosis. This discovery was made recently by scientists from Institut Pasteur, who used a mouse model to investigate co-infection by mycobacteria and helicobacter.
"We now know that the emergence of diseases is a complex phenomenon which is not governed by the simple equation whereby a pathogen leads to disease," explains Claude Leclerc, Head of the Immune Regulation and Vaccinology Unit at the Institut Pasteur. "We know that there can be interferences between the immune control of bacterial or viral infections in case of concomitant or successive infections/colonization with other pathogens. That is why we have been interested in the possible interactions between symptoms resulting from Mycobacterium tuberculosis infection and the natural pre-colonization with other bacteria, a domain which had previously received little scientific attention."
The latent M. tuberculosis infection affects 30% of the global population. Most of the time, people who have contracted the bacteria do not develop active disease. "In specific pathogenic-free mice, M. tuberculosis infection is generally well controlled. However, mice precolonized naturally with Helicobacter hepaticus develop highly aggravated tuberculosis symptoms, which are correlated with a significant modification of the intestinal microbiota," says Laleh Majlessi, a scientist in the Integrated Mycobacterial Pathogenomics Unit at the Institut Pasteur. These observations have highlighted a possible link between Helicobacter hepaticus pre-colonization, the modification of the gut microbiota and the drastic decrease in the immune control of the growth of M. tuberculosis in the lungs.
"We also know that HIV weakens the immune system and can lead to severe TB," adds Claude Leclerc. Epidemiological and experimental observations by the two teams demonstrated that, in mice, the natural colonization of the digestive tract by H. hepaticus coincides with changes to the intestinal microbiota and the emergence of inflammation, followed by a drastic deterioration in immune control of the proliferation of M. tuberculosis administered subsequently. "Our findings indicated that the H. hepaticus colonization prevents the induction of effective immune responses against M. tuberculosis" explain the scientists. "The proliferation of mycobacteria, usually well controlled in mice, increased drastically in co-infected animals to reach bacterial loads 1,000 times more than usual!" This led to uncontrolled inflammation and dramatic lung tissue destruction.
These results show that the impact of chronic microbial colonization by Helicobacter spp. (equivalent of Helicobacter pylori in humans) and subsequent infection by M. tuberculosis may be greater than previously thought. The finding is especially significant since the two species are among the most widespread invasive bacteria in human populations. It also suggests – even if more detailed research still needs to be conducted in humans – that the infection by Helicobacter pylori of TB carriers could have an impact on the occurrence of active tuberculosis.
Colonization with Helicobacter is concomitant with modified gut microbiota and drastic failure of the immune control of Mycobacterium tuberculosis. Mucosal Immunol. February 1st, 2017.
L Majlessi1,2,3, F Sayes1,2,3, J-F Bureau4, A Pawlik1, V Michel5,6, G Jouvion7,8, M Huerre8,9, M Severgnini10, C Consolandi10, C Peano10, R Brosch1, E Touati5,6 and C Leclerc2,3
1. Institut Pasteur, Integrated Mycobacterial Pathogenomics Unit, Paris, France
2. Institut Pasteur, Immune Regulation and Vaccinology Unit, Paris, France
3. INSERM U1041, Paris, France
4. Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Paris, France
5. Institut Pasteur, Helicobacter Pathogenesis Unit, Paris, France
6. CNRS ERL3526, Paris, France
7. Institut Pasteur, Human Histopathology and Animal Models Unit, Paris, France
8. Institut Pasteur, Histotechnology and Pathology Research and Expertise Unit, Paris, France
9. Institut Curie, Pathology Department, Paris, France
10. Institute of Biomedical Technologies, CNR, Segrate, Milan, Italy