A co-evolutionary perspective on humans and Mycobacterium tuberculosis in the era of systems biology
- NIHR Biomedical Research Centre, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, United Kingdom
- Institute for Life Sciences, United Kingdom
- Africa Health Research Institute, South Africa
- College of Health Sciences, School of Laboratory Medicine and Medical Sciences, University of KwaZulu Natal, South Africa
- Department of Infection and Immunity, University College London, United Kingdom
Figures
Figure 1
Multiple pathways can lead to tuberculosis (TB) disease from opposing immunological extremes.
Generally, these can be viewed as immune deficiencies or immune excess, but the majority of patients who develop TB are relatively young with a competent immune response, illustrating the complexity of this spectrum. Though not quantitative, font size relates to contribution to global incidence. Left arrow: Ghon focus at lung base; Right arrow: cavity at lung apex.
Figure 2
Selection pressure of prolonged co-evolution favors individuals permissive to asymptomatic Mycobacterium tuberculosis (Mtb) colonization but resistant to active disease.
Over millennia, Mtb circulation in society will remove genetic traits that cause high susceptibility to active tuberculosis (TB) infection. Perhaps less intuitively, if Mtb generates trained immunity that protects against other fatal diseases, individuals with low susceptibility to initial Mtb infection will also be selected against due to increased mortality from other infections. The resulting population would then reflect modern humans: highly susceptible to initial Mtb colonization but with low susceptibility to TB disease. The figure illustrates the selective pressure concept, the increase in risk is not binary but gradual, with susceptibility determined by multiple aspects of the host immune response.
Figure 3
Schematic of the interactions needed for Mycobacterium tuberculosis (Mtb) to escape the host immune response.
As control of Mtb requires a coordinated host response, there are multiple sequences of immune events that can ultimately result in progression to active tuberculosis (TB) disease. A major immune disturbance, such as TNF-α or PD-1 inhibition, gives a relatively direct pathway to active TB. However, most individuals develop TB due to a series of less apparent immune events and no clear global immune disturbance that can be identified by current immune profiling approaches.
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A co-evolutionary perspective on humans and Mycobacterium tuberculosis in the era of systems biology
eLife 14:RP108175.
https://doi.org/10.7554/eLife.108175.3
