Killing Mycobacterium tuberculosis in vitro: What model systems can teach us

Tracy L. Keiser, Georgiana E. Purdy

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Mycobacterium tuberculosis 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 M. tuberculosis 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 (1). In addition, genomic analysis demonstrated that genetic expansion of the mycobacterial repertoire coincided with the geographical expansions of humans, solidifying the evidence that M. tuberculosis has evolved with its host (2). During this evolution, M. tuberculosis has developed numerous ways to subvert the human immune response (3 - 5). For instance, a hallmark of M. tuberculosis 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) (6). Ideally, bacteria are killed and degraded upon phagosome-lysosomal fusion, and as antigen-presenting cells (APCs), macrophages present M. tuberculosis peptides and lipid antigens, ultimately leading to a highly specific adaptive immune response. Therefore, the primary encounter between M. tuberculosis 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.

Original languageEnglish (US)
Title of host publicationTuberculosis and the Tubercle Bacillus
Subtitle of host publicationSecond Edition
Publisherwiley
Pages541-556
Number of pages16
ISBN (Electronic)9781683670834
ISBN (Print)9781555819552
DOIs
StatePublished - Sep 5 2017

Keywords

  • Antigen-presenting cells
  • In vitro models
  • Induced pluripotent stem cells
  • Mycobacterium tuberculosis
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Medicine(all)

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