M. tuberculosis induces selective upregulation of Toll-like receptors in the mononuclear leukocytes of patients with active pulmonary tuberculosis

TL;DRAbstract

Human and mouse studies indicate that Toll-like receptors (TLR) are important in mycobacterial infections. We investigated TLR gene expression in fresh unstimulated blood and bronchoalveolar lavage (BAL) from patients with pulmonary tuberculosis, using a well-validated real time PCR. A splice variant of TLR1, designated hsTLR1, was found in all donors tested. hsTLR1 mRNA lacks exon 2, which is a 77 bp region of the 5/ untranslated region, but contains the same coding sequence as TLR1. Compared to the matched controls, whole blood from patients had increased levels of mRNA encoding TLR2 (p = 0.0006), TLR1 (p = 0.004), hsTLR1 (p = 0.0003), TLR6 (p < 0.0001) and TLR4 (p = 0.0002). By contrast, expression of these TLR was not increased in BAL. An increased level of hsTLR1 mRNA was found in both CD3- (p = 0.0078) and in CD4+ cells (p = 0.028) resulting in an increased ratio of hsTLR1 mRNA to TLR1 and to TLR6 mRNA. An in vitro study in THP1 cells suggested that this relative increase in h

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