PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Abstract

To understand functional role of PD‐1‐expressing MAIT cells during tuberculosis infection in humans, sorted PD‐1+ and PD‐1− MAIT cells from pleural effusions of patients with pleural tuberculosis were subjected to transcriptome sequencing. PD‐1‐expressing MAIT cells were analysed by flow cytometry and their phenotypic and functional features were investigated. Transcriptome sequencing identified 144 genes that were differentially expressed between PD‐1+ and PD‐1− MAIT cells from tuberculous pleural effusions and CXCL13 was the gene with highest fold difference. The level of PD‐1‐expressing MAIT cells was associated with extent of TB infection in humans. PD‐1‐expressing MAIT cells had increased production of CXCL13 and IL‐21 as determined by flow cytometry. PD‐1highCXCR5− MAIT cells were significantly expanded in pleural effusions from patients with pleural tuberculosis as compared with those from peripheral blood of both patients with tuberculosis and healthy controls. Although PD‐1highCXCR5− MAIT cells from tuberculous pleural effusions had reduced IFN‐γ level and increased expression of Tim‐3 and GITR, they showed activated phenotype and had higher glucose uptake and lipid content. It is concluded that PD‐1‐expressing MAIT cells had reduced IFN‐γ level but increased production of both CXCL13 and IL‐21.

Efficient 5-OP-RU-Induced Enrichment of Mucosa-Associated Invariant T Cells in the Murine Lung Does Not Enhance Control of Aerosol Mycobacterium tuberculosis Infection

“…Further, we show that while MAIT cells are activated and expand early in P2C/5-OP-RU infected mice, they are subsequently depleted and driven to functional exhaustion. These results mirror observations of peripheral MAIT cell depletion and upregulation of exhaustion markers during active TB infection in humans (12,13,17). We also highlight that neither decreasing Mtb inoculum nor the time between priming and infection impacted bacteriologic outcomes.…”

“…MAIT cell responses have been documented in a number of infectious and non-infectious inflammatory diseases (2,11), including the leading infectious cause of death globally, tuberculosis (TB) (3,(12)(13)(14)(15)(16)(17)(18)(19). Peripheral blood MAIT cells contract during active TB disease (13,17,18,20) and are activated during acute exposure in healthy household contacts (3,15).…”

The Roles of Chemokines in Immune Response to Mycobacterial Infection

“…A recent study suggests that adenosine deaminase (ADA), interferon (IFN)-γ, and interleukin (IL)-27 show high diagnostic accuracy in TB pleural effusion; however, the profiles of C-X-C motif chemokine ligand 9 (CXCL9), CXCL11, and CXCL12 need to be further examined to prove their diagnostic values in TB pleural effusion (51). In addition, PD-1-expressing mucosal-associated invariant T (MAIT) cells showed increased levels of both CXCL13 and IL-21, and associated with the disease severity of TB pleurisy in the patients (52). CXCL13 is important for the recruitment of CXCR5+ B cells and Tfh to the lymphoid follicles for T-B cell interactions (53) and recognizes CXCR5, a marker for T follicular helper (Tfh) cells (54).…”

Functional and Activation Profiles of Mucosal-Associated Invariant T Cells in Patients With Tuberculosis and HIV in a High Endemic Setting

“…It is possible that this diminished functional capacity is due to inhibition resulting from increased expression of inhibitory receptors such as PD1 and TIM-3 (34)(35)(36). We investigated whether PD1 expression could be a contributing factor as previously described (21,30,37). We found that resting MAIT cells in our disease groups were significantly more activated than healthy controls, and that in TB disease (active TB and HIV-associated TB) MAIT cells expressing IFNγ following mycobacterial stimulation, were more activated than healthy controls.…”