Chapter 25 : Killing : What Model Systems Can Teach Us

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is one of the oldest and most successful pathogens in human history due in large part to its coevolution with humans, resulting in an exquisite adaptation by the bacterium to its host. Detection of DNA in mummified human remains from both the Old and New World is evidence that tuberculosis (TB) has been part of our history for millennia ( ). In addition, genomic analysis demonstrated that genetic expansion of the mycobacterial repertoire coincided with the geographical expansions of humans, solidifying the evidence that has evolved with its host ( ). During this evolution, has developed numerous ways to subvert the human immune response ( ). For instance, a hallmark of pathogenicity is its ability to establish a niche in macrophages, the host immune cells that should be the bacterium’s ultimate undoing. Macrophages are a crucial cell subset of the innate immune system whose primary function is to patrol the host and seek out foreign particles. Bacteria and other pathogens are recognized via their pathogen-associated molecular patterns, which initiate a signaling cascade that results in phagocytosis of the pathogen and upregulation of a proinflammatory response. The most notable cytokines produced by macrophages associated with this proinflammatory state in TB are interleukin-1 (IL-1), IL-6, IL-8, IL-12, and tumor necrosis factor (TNF) ( ). Ideally, bacteria are killed and degraded upon phagosome-lysosomal fusion, and as antigen-presenting cells (APCs), macrophages present peptides and lipid antigens, ultimately leading to a highly specific adaptive immune response. Therefore, the primary encounter between and macrophages dictates the subsequent immune response. In TB, this immune response is focused on containment and eventual eradication of the bacterium in the granuloma.

Citation: Keiser T, Purdy G. 2017. Killing : What Model Systems Can Teach Us, p 541-556. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0028-2016
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