Impaired toll like receptor 9 response in pulmonary tuberculosis

Innate immune responses are important in susceptibility to pulmonary tuberculosis (TB). In order to test the hypothesis that Toll-like receptor (TLR) 2 function would be abnormal in patients with active pulmonary TB we compared the cytokine responses of peripheral blood mononuclear cells (PBMC) to innate immune ligands in a case-control study.

PBMC from 19 untreated pulmonary TB patients, 17 healthy controls, and 11 treated pulmonary TB patients, were cultured for 24h with TLR 2 ligand (PAM-CSK) and other TLR ligands (muramyl dipeptide, flagellin, lipopolysaccharide (LPS), CpG oligodeoxynucleotide (CpG-ODN)). Interleukin-8 (IL-8) was estimated in the supernatant by ELISA. Messenger RNA expression for inflammatory cytokines was quantitated using real time PCR.

The important findings were (1) reduced PBMC secretion of IL-8 in response to all ligands in active TB; (2) normal to increased PBMC secretion of IL-8 in response to all ligands except CpG ODN (TLR 9 ligand) in TB patients who had recovered; (3) absence of difference in mRNA expression for a consortium of inflammatory pathway genes between healthy controls, active pulmonary tuberculosis and treated pulmonary tuberculosis patients.

There was a generalized post-translational suppression of the IL-8 response to innate immune ligands in active TB. There appears to be a defect of TLR 9 signaling in patients with tuberculosis, the nature of which needs to be further explored.