title: Associations between toll-like receptors and interleukin-4 in the lungs of patients with tuberculosis.
abstract: 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.
authors.affiliation: Departments of Medical Biochemistry and Anatomical Pathology, University of Stellenbosch, Cape Town, South Africa.
authors.forename: Gael
authors.initials: G
authors.lastname: Fenhalls
authors.forename: Ginette R
authors.initials: GR
authors.lastname: Squires
authors.forename: Liesel
authors.initials: L
authors.lastname: Stevens-Muller
authors.forename: Juanita
authors.initials: J
authors.lastname: Bezuidenhout
authors.forename: Gillian
authors.initials: G
authors.lastname: Amphlett
authors.forename: Ken
authors.initials: K
authors.lastname: Duncan
authors.forename: Pauline T
authors.initials: PT
authors.lastname: Lukey
mesh_terms: D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity; D015415:Biomarkers; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009336:Necrosis; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D015847:Interleukin-4