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

Hendrik J Nel,Gerhard Walzl,Nelita Du Plessis,Paul D Van Helden,André G Loxton,Leanie Kleynhans

doi:10.1186/1471-2180-14-9

Hendrik J Nel, Gerhard Walzl + Show 4 more

Open Access

https://doi.org/10.1186/1471-2180-14-9

Copy DOI

Abstract

BackgroundThe 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.ResultsWe 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.ConclusionOur 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.

Highlights

The global epidemiology of parasitic helminths and mycobacterial infections display extensive geographical overlap, especially in the rural and urban communities of developing countries
M. bovis BCG clearance and lung pathology is not influenced by an established or successive T. muris infection The influence of T. muris infection on host ability to control a chronic, low grade M. bovis BCG infection in BALB/c mice was investigated for both experimental protocols (Figure 1A and B)
Results demonstrated that an ongoing helminth-induced T helper 2 (TH2) immune background, pre-established by T. muris trickle infection, failed to alter mycobacterial proliferation and dissemination when compared to M. bovis BCG-only infected mice in the lungs (Figure 2A) and spleen

Summary

Introduction

The global epidemiology of parasitic helminths and mycobacterial infections display extensive geographical overlap, especially in the rural and urban communities of developing countries. Protective immune responses to M. tb infection are associated with enhanced T helper 1 (TH1) type cellular immunity and the production of characteristic TH1 cytokines such as tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-12 (IL-12) [8]. Since TH1 and TH2 immune responses have the ability to concurrently downregulate each other, a state of co-infection could result in inappropriate protective host immune responses to either infections [11]. Both pathogens have the potential to induce regulatory T cell (Treg) responses associated with production of immune suppressive cytokines such as IL-10 and transforming growth factor beta (TGF-β) [10,11,12,13]

Methods

Results

Discussion

Conclusion