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Associations between Toll-Like Receptors and Interleukin-4 in the Lungs of Patients with Tuberculosis

MRC Center for Molecular and Cellular Biology, and Departments of Medical Biochemistry and Anatomical Pathology, University of Stellenbosch, Cape Town, South Africa; and Asthma Cell Biology, Statistical Sciences, and Diseases of the Developing World, GlaxoSmithKline R&D, Stevenage, United Kingdom

Address correspondence to: Pauline Lukey, Ph.D., Diseases of the Developing World, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. E-mail: pauline.t.lukey{at}gsk.com

Toll-like receptors (TLRs) are implicated in the intracellular killing of Mycobacterium tuberculosis, and their expression is modulated by interleukin-4 (IL-4) in vitro. Our aim was to examine the expression of TLRs at the site of pathology in tuberculous lung granulomas and to explore the effect of the immune response on TLR expression. Immunohistochemistry was performed on lung granulomas from nine patients with tuberculosis undergoing lobectomy for haemoptysis. All nine patients expressed all of the TLRs studied (TLRs 1–5 and 9), whereas only five out of the nine patients had any granulomas positive for IL-4. Statistical analysis of TLR and cytokine staining patterns in 183 individual granulomas from the nine patients revealed significant associations between pairs of receptors and IL-4. A positive association between TLR2 and TLR4 (P < 0.0001) and a negative association between TLR2 and IL-4 (P < 0.0001) was observed. The associations between TLRs 1, 5, and 9 were significantly different in IL-4–negative compared with IL-4–positive patients. In conclusion, TLRs are expressed by various cell types in the human tuberculous lung, and their expression patterns are reflected by differences in the immune response.

Abbreviations: acid-fast bacilli, AFB • dendritic cells, DCs • interferon, IFN • interleukin, IL • lipopolysaccharide, LPS • purified protein derivative, PPD • T helper, Th • Toll-like receptors, TLRs • tumor necrosis factor, TNF

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