Abstract
Transmission of Mycobacterium tuberculosis bacilli from one individual to another is the basis of the disease process. While considerable emphasis has been placed on the role of host mechanisms of resistance in establishing or preventing new infection, far less has been expended on understanding possible factors operative at the bacterial level. In this study we established a panel of clinical isolates of M. tuberculosis strains obtained from the Western Cape region of South Africa, each of which had been carefully tracked in terms of their degree of transmission in the community. Each of the panel were used to infect guinea pigs with 15–20 bacilli by aerosol exposure and the course of the infection then determined. Strains with different degrees of transmission could not be distinguished in terms of their capacity to grow in the main target organs of infected animals. However, rather surprisingly, while strains with no evidence of transmission [NOT] in general caused moderate to severe lung damage, this parameter in animals infected with highly transmitted [HT] strains was mostly mild. In terms of TH1 immunity these signals were strongest in these latter animals, as was IL-17 gene expression, whereas minimal signals for regulatory molecules including IL-10 and FoxP3 were seen across the entire panel. In terms of T cell numbers, responses of both CD4 and CD8 were both far faster and far higher in animals infected with the HT strains. At the gene expression level we observed a major three-fold difference [both up and down] between NOT and HT strains, but in terms of proteins of key interest only a few [including PD-L1 and HIF-3] showed major differences between the two groups. Overall, it was apparent that NOT strains were far more inflammatory that HT strains, and appeared to trigger a much larger number of genes, possibly explaining the observed damage to the lungs and progressive pathology. In contrast, the HT strains, while equally virulent, were more immunogenic and developed much stronger T cell responses, while keeping lung damage to a minimum. Hence, in terms of trying to explain the capacity of these strains to cause transmission, these results are clearly paradoxical.
Highlights
Tuberculosis, the number one cause of death from an infectious disease caused by a single pathogen [1], transmitted by coughing after the bacillus is exhaled from the infected lung
We had predicted that HT strains would cause the most lung damage, allowing them to escape the lungs, but the results suggested the reverse
The objective of this study was to determine if differences could be observed in the host response in the guinea pig to infection with isolates of M. tuberculosis that differ in their known transmission histories
Summary
Tuberculosis, the number one cause of death from an infectious disease caused by a single pathogen [1], transmitted by coughing after the bacillus is exhaled from the infected lung. More recently attempts have been made in terms of inter-species models – non-human primates to guinea pigs – and within single species [mixing infected and healthy cattle for example] At this time no new information seems to have come out of these approaches. A further element of disease transmission which has rarely been addressed to date, is the intrinsic nature of the M. tuberculosis isolate itself in terms of its actual ability to be transmitted In this regard, it is evident that, apparently independently of which family a given isolate belongs to, certain isolates appear to undergo very substantial transmission through communities, whereas others show very little transmission, if any at all [“unique” or “no observed transmission, NOT]. What these properties might be is unknown, for the simple reason that while thousands of isolates have undergone molecular genotyping, only a very few have ever been tested in animal models in which the host response to these isolates can be compared
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
