Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a major health problem, with 10 million new cases diagnosed each year. Innate immunity plays an important role in the host defense against M. tuberculosis, and the first step in this process is recognition of MTB by cells of the innate immune system. Several classes of pattern recognition receptors (PPRs) are involved in the recognition of M. tuberculosis, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nod-like receptors (NLRs). Among the TLR family, TLR2, TLR4, and TLR9 and their adaptor molecule MyD88 play the most prominent roles in the initiation of the immune response against tuberculosis. In addition to TLRs, other PRRs such as NOD2, Dectin-1, Mannose receptor, and DC-SIGN are also involved in the recognition of M. tuberculosis. Human epidemiological studies revealed that genetic variation in genes encoding for PRRs and downstream signaling products influence disease susceptibility, severity, and outcome. More insight into PRRs and the recognition of mycobacteria, combined with immunogenetic studies in TB patients, does not only lead to a better understanding of the pathogenesis of tuberculosis but also may contribute to the design of novel immunotherapeutic strategies.
Highlights
Tuberculosis (TB) is a major public health problem, with 10 million new cases diagnosed each year, causing a death toll of 2 million victims
The role of inborn variability in susceptibility to tuberculosis has been accidentally proven by an episode that occurred almost a century ago, when in 1926 newborn infants from the town of Lubeck in Germany received live Mycobacterium tuberculosis (MTB) instead of the vaccine bacillus CalmetteGuerin (BCG)
This paper focuses on the role of the pattern recognition receptors (PRRs) and downstream signaling for the recognition of MTB, including the intracellular mechanisms activated by PRRs
Summary
Tuberculosis (TB) is a major public health problem, with 10 million new cases diagnosed each year, causing a death toll of 2 million victims. The first step is the recognition of mycobacteria as invading pathogens, followed by activation of innate host defense responses, and the subsequent initiation of adaptive immune responses. Knowledge about these processes is crucial for understanding the pathophysiology of tuberculosis, on the one hand, and for the development of novel strategies of vaccination and treatment such as immunotherapy on the other hand. Two-to-three weeks after infection, T-cell immunity develops and antigen-specific T lymphocytes arrive, proliferate within the early lesions or tubercles, and release proinflammatory cytokines such as interferonγ (IFNγ) that will activate macrophages to kill the intracellular mycobacteria. We will discuss the human genetic studies done to assess the role of variation in PRR genes for the susceptibility to tuberculosis
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