Dendritic cells in the lung cavities of extensively drug-resistant tuberculosis patients exhibit altered frequency and phenotype

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Background: Studies examining dendritic cell (DC) immunobiology in tuberculosis (TB) patients have been conflicting, and no studies have examined DCs in the peripheral blood or lungs of patients with pre- or extensively drug-resistant TB (XDR-TB). Methods: To provide insight into DC immunobiology, we first compared the DC subsets in the peripheral blood of XDR-TB patients with that from participants with latent TB infection (LTBI). Second, we compared DC subsets from cavity biopsies from explanted lung sections with normal-appearing lung tissue from pre-XDR/XDR-TB patients undergoing resection surgery. DCs were assessed for phenotypic and functional markers using flow cytometry. Results: In the peripheral blood of XDR-TB patients, plasmacytoid DCs (pDCs) expressed lower levels of cluster of differentiation 83 (CD83; p=0.01), toll-like receptor 2 (TLR-2; p<0.0001) and macrophage mannose receptor (MMR; p<0.0001), with higher levels of programmed cell death protein 1 (PD-L1; p=0.007) than pDCs from LTBI participants (p=0.01). MMR expression from the conventional DC1 (cDC1) subset in XDR-TB patients was found to be higher (p=0.02) than that from the cDC1 subset in LTBI participants. In the lung compartment (cavity and normal-appearing lung), the dominant DC subset was the pDCs (p=0.02), despite the conventional DC subsets (cDCs) expressing higher levels of C-C chemokine receptor 7 (CCR7) (p=0.02 for both comparisons), CD83 (p≤0.03 for both comparisons), TLR-2 (p=0.02 for both comparison), MMR (p=0.02 for both comparisons) and DC-SIGN (p≤0.05 for both comparisons). Conclusions: The low frequency of cDCs in the lung cavity of XDR-TB patients in conjunction with the limited migratory and co-stimulatory expression of pDCs suggests that there is DC dysregulation in the lung mucosal milieu, possibly due to persistent disease.

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