MRC National Institute for Medical Research, London
Science for Health
Different TB strains elicit different immune responses
07 March 2011
Mycobacterium tuberculosis is a long-standing human pathogen spread by aerosol transmission between individuals interacting in close social groups. High-throughput sequence analysis has allowed reconstruction of the evolution of human Mycobacterium tuberculosis Complex (MTBC), differentiating the bacteria into six main phylogenetic lineages. Three lineages, including two whose members are known as M. africanum, branched off from a common ancestor at an early stage of evolution. They are referred to as evolutionarily 'ancient' lineages. Three separate evolutionarily 'modern' lineages diverged at a later time. It is thought that the evolution of M. tuberculosis parallels the evolution of human societies, and the phylogeny as determined by whole genome sequencing of clinical isolates is indeed consistent with emergence of the pathogen with modern humans in Africa and its subsequent dissemination along routes of human migration and trade.
Tuberculosis lineages
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Ancient lineages began to diversify at an early stage of human evolution, migrating within and out of Africa. Modern lineages were carried by humans migrating north from Africa, and diversified at a later stage of human evolution.
This phylogeny provides a rational framework to assess whether the genotypic diversity of MTBC is associated with diversity in biological phenotype. Douglas Young (pictured) and Sebastien Gagneux, both from NIMR's Division of Mycobacterial Research, used a collection of strains covering the global genetic diversity of MTBC to test the hypothesis that inflammatory phenotype would be linked to genotype. They explored the interaction of different M. tuberculosisisolates with the innate immune system, which plays important contrasting roles in initial resistance to infection and in disease transmission.
They found that there is a difference in the innate immune response between isolates belonging to 'modern' lineages that have evolved amongst high-density populations in regions of recent massive demographic expansion, and isolates belonging to 'ancient' lineages selected in older low-density human populations.
Our results provide insights into host-pathogen co-evolution and into fundamental mechanisms underlying the pathogenesis of M. tuberculosis. To our knowledge, this is the first time that the immune response to a particular infectious agent has been measured in a systematic manner by selecting representative strains belonging to the major human MTBC lineages and grasping the global M. tuberculosis genetic diversity, including notably M. africanum. As we show here, the combination of genotypic, phenotypic and epidemiological studies offers the potential for novel insights into the biology of this pathogen.
Douglas Young and Sebastien Gagneux
Original article
Damien Portevin, Sébastien Gagneux, Iñaki Comas, and Douglas Young (2011)
Human macrophage responses to clinical isolates from the Mycobacterium tuberculosis complex discriminate between ancient and modern lineages
PLoS Pathogens 7(3): e1001307. Full-text.
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