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Immunology of tuberculosis

Lee W Riley, MD
Section Editor
C Fordham von Reyn, MD
Deputy Editor
Elinor L Baron, MD, DTMH


The human host serves as the only natural reservoir for Mycobacterium tuberculosis. The ability of the organism to efficiently establish latent infection has enabled it to spread to nearly one-third of the world's population [1]. According to the 2017 World Health Organization report, in 2016, an estimated 6.3 million new cases of tuberculosis and 1.3 million deaths among HIV-uninfected people were reported worldwide [2]. The progression from latent tuberculosis infection to active disease remains poorly understood. Given the magnitude of the health problem and the emergence of drug-resistant strains of the organism, a better understanding of the immunology of this disease and the development of an effective vaccine are highly desirable. (See "Epidemiology of tuberculosis".)

The immunology of M. tuberculosis will be reviewed here. The microbiology and pathogenesis of this infection, including virulence factors, tropism for the lungs, and latency factors, are discussed separately. (See "Natural history, microbiology, and pathogenesis of tuberculosis".)


The majority of individuals in the general population who become infected with M. tuberculosis never develop clinical disease [3]. This demonstrates that the innate and adaptive immune response of the host in controlling tuberculosis (TB) infection is effective. Mycobacterial and host factors that adversely affect these two arms of the immune system contribute to latent tuberculosis infection (LTBI) and active disease.

Host factors

Innate immunity — The pathophysiology of innate immune response during first encounter of M. tuberculosis with lung cells remains poorly characterized. In the average human alveolus, there are more than 28,000 epithelial cells (pneumocytes) and about 50 macrophages [4,5]. Mouse studies have shown that after about 14 days of infection, the predominant cell type infected with M. tuberculosis is the myeloid dendritic cell rather than the alveolar macrophage [6]. Thus, during the very early phase of lung infection, the interaction of M. tuberculosis with lung epithelial cells may affect later dendritic cell and alveolar macrophage migration and ultimately clinical outcome. Little is known about what happens during this early phase.

Once M. tuberculosis comes into contact with dendritic or alveolar macrophages, the interaction of these cells with M. tuberculosis first involves recognition by these cells of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) located on the cell surface or in the cytosol [7]. Distinct sets of macrophage PRRs recognize distinct sets of MAMPs of M. tuberculosis. These PRRs serve to trigger innate immune response against molecules recognized to be foreign to the host cell. The recognition of M. tuberculosis by a group of PRRs called toll-like receptors (TLRs) triggers cell signal transduction that induces a proinflammatory response that is supposed to control the infection [8]. However, M. tuberculosis has evolved to subvert these host responses for its own survival in the host.

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Literature review current through: Nov 2017. | This topic last updated: Nov 30, 2017.
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