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Trehalose Dimycolate (Cord Factor) as a Contributing Factor to Tuberculosis Pathogenesis

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Tuberculosis Host-Pathogen Interactions

Abstract

This chapter examines mycobacterial glycolipid trehalose 6,6’-dimycolate (TDM; cord factor) as it relates to the development of tuberculosis (TB) pathogenesis. TDM, a major surface glycolipid, is recognized as the most widely studied “virulence factor” of Mycobacterium tuberculosis (MTB). It is the most abundant glycolipid on the surface of mycobacterial species and contributes to organism morphology. Although it is known to play multiple roles in models of TB pathogenesis, direct understanding of how it leads to development of clinical disease states during tuberculosis disease is not yet clear. TDM induces the production of proinflammatory cytokines and chemokines from innate macrophages. It can also induce defined lung pathologies to mimic many aspects of primary MTB infection, including induction of activated foreign body granulomas and pneumonitis in naïve mice, and hypersensitive immune granulomas or hyper-coagulation in sensitized mice. Identification of numerous potential host receptors for this glycolipid has triggered renewed investigation into the importance of TDM in the clinical manifestation of disease. Here, a historical review is presented to support regulated innate and adaptive immune responses to cord factor which have potential to affect development of related pathologies. Examination of recent hypotheses that link its physical structure to development of post primary disease is also discussed.

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Acknowledgements

A special note of appreciation goes to colleagues Shen-An Hwang, PhD, Chinnaswamy Jagannath, PhD, and Robert L. Hunter, MD, PhD, for their discussions and insights.

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  1. Department of Pathology and Laboratory Medicine, University of Texas-Houston McGovern Medical School, Houston, TX, USA

    Jeffrey K. Actor

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  1. Department of Microbial Pathogenesis and Immunology, Texas A&M University College of Medicine, Bryan, TX, USA

    Jeffrey D. Cirillo

  2. The University of Tennessee Health Science Center, Memphis, TN, USA

    Ying Kong

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Actor, J.K. (2019). Trehalose Dimycolate (Cord Factor) as a Contributing Factor to Tuberculosis Pathogenesis. In: Cirillo, J., Kong, Y. (eds) Tuberculosis Host-Pathogen Interactions. Springer, Cham. https://doi.org/10.1007/978-3-030-25381-3_3

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