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Published ahead of print on December 30, 2002, doi:10.1165/rcmb.2002-0163OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 1, July 2003, 28-38

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Submitted on August 23, 2002
Revised on December 27, 2002

Associations between Toll-like Receptors and IL-4 in the Lungs of Patients with Tuberculosis

Gael Fenhalls1, Ginette R Squires2, Liesel Stevens-Muller1, Juanita Bezuidenhout3, Gillian Amphlett4, Ken Duncan5, and Pauline T Lukey5*

1 Medical Biuochemistry, University of Stellenbosch, Cape Town, Western Cape, South Africa; Molecular and Cellular Biology, Medical Research Council, Cape Town, Western Cape, South Africa, 2 Asthma Cell Biology, GlaxoSmithKline R and D, Stevenage, Hertfordshire, United Kingdom, 3 Anatomical Pthology, University of Stellenbosch, Cape Town, Western Cape, South Africa, 4 Statistical Sciences, GlaxoSmithKline R and D, Stevenage, Hertfordshire, United Kingdom, 5 Diseases of the Developing World, GlaxoSmithKline R and D, Stevenage, Hertfordshire, United Kingdom

* To whom correspondence should be addressed. 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 (TLRs1 - 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 to 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.




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