Mycobacterium bovis BCG infection severely delays Trichuris muris expulsion and co-infection suppresses immune responsiveness to both pathogens

Abstract
Background: The global epidemiology of parasitic helminths and mycobacterial infections display extensive geographical overlap, especially in the rural and urban communities of developing countries. We investigated whether co-infection with the gastrointestinal tract-restricted helminth, Trichuris muris, and the intracellular bacterium, Mycobacterium bovis (M. bovis) BCG, would alter host immune responses to, or the pathological effect of, either infection. Results: We demonstrate that both pathogens are capable of negatively affecting local and systemic immune responses towards each other by modifying cytokine phenotypes and by inducing general immune suppression. T. muris infection influenced non-specific and pathogen-specific immunity to M. bovis BCG by down-regulating pulmonary TH1 and Treg responses and inducing systemic TH2 responses. However, co-infection did not alter mycobacterial multiplication or dissemination and host pulmonary histopathology remained unaffected compared to BCG-only infected mice. Interestingly, prior M. bovis BCG infection significantly delayed helminth clearance and increased intestinal crypt cell proliferation in BALB/c mice. This was accompanied by a significant reduction in systemic helminth-specific TH1 and TH2 cytokine responses and significantly reduced local TH1 and TH2 responses in comparison to T. muris-only infected mice. Conclusion: Our data demonstrate that co-infection with pathogens inducing opposing immune phenotypes, can have differential effects on compartmentalized host immune protection to either pathogen. In spite of local and systemic decreases in TH1 and increases in TH2 responses co-infected mice clear M. bovis BCG at the same rate as BCG only infected animals, whereas prior mycobacterial infection initiates prolonged worm infestation in parallel to decreased pathogen-specific TH2 cytokine production.
Description
Publication of this article was funded by the Stellenbosch University Open Access Fund.
Nel, H. et al. 2014. Mycobacterium bovis BCG infection severely delays Trichuris muris expulsion and co-infection suppresses immune responsiveness to both pathogens. BMC Microbiology, 14:9, doi:10.1186/1471-2180-14-9.
The original publication is available at http://www.biomedcentral.com/bmcmicrobiol/
Keywords
Tuberculosis -- Etiology, Communicable diseases -- Diagnosis -- Developing countries, Tuberculosis -- Immunological aspects, Tuberculosis -- Effect of helminthiasis on, Trichuris muris -- Immunological aspects, Mycobacterium bovis (M. bovis) -- Immunological aspects, Communicable diseases -- Transmission -- Developing countries -- Research, Immune response
Citation
Nel, H. et al. 2014. Mycobacterium bovis BCG infection severely delays Trichuris muris expulsion and co-infection suppresses immune responsiveness to both pathogens. BMC Microbiology, 14:9, doi:10.1186/1471-2180-14-9.