Inhibition of toll-like receptor 2 (TLR-2)-mediated response in human alveolar epithelial cells by mycolic acids and Mycobacterium tuberculosismce1 operon mutant

• Published in: Pathogens and disease Vol. 70; no. 2; pp. 132 - 140
• Main Authors: Sequeira, Patricia C., Senaratne, Ryan H., Riley, Lee W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2014; Oxford University Press
• Subjects: Tuberculosis; alveolar epithelial cells; mycolic acid; A549 cells; operon; tuberculosis
• ISSN: 2049-632X
• DOI: 10.1111/2049-632X.12110

Abstract In human lungs, the earliest encounter of Mycobacterium tuberculosis, the agent of tuberculosis, involves alveolar epithelial cells. Droplets expectorated by a patient with tuberculosis are likely to contain a mixed population of M. tuberculosis cells in different physiologic and metabolic states from the lung lesions of the patient. Here, we compared the chemokine expression patterns of human epithelial cell line A549 and RAW 264.7 macrophage cells infected with wild-type M. tuberculosis H37Rv against patterns induced by a mutant that accumulates free mycolic acids in its cell wall (Δmce1). We also examined the effect of free mycolic acids on toll-like receptor-2 (TLR-2). Wild-type M. tuberculosis induced significantly higher levels of IL-8, MCP-1, RANTES, and IP-10 in both cell types than did Δmce. Free mycolic acids reduced the ability of the mammalian cells to respond to a TLR-2 agonist in a dose-dependent manner. These observations suggest that differences in mycolic acid abundance in the M. tuberculosis cell wall can affect TLR-2-mediated pro-inflammatory response in both epithelial and macrophage cells. The final fate of a new infection may be ultimately determined by the proportion of M. tuberculosis cells expressing free mycolates in the infecting inoculum population. A type of fatty acid called mycolic acid made by the bacteria that causes TB inhibits lung cell function, which may ultimately determine if someone gets TB or not.