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

Jing Jiang1, Zhihong Cao2, Jiuxin Qu1

  • 1Department of Laboratory Medicine, Shenzhen Third People's Hospital, and Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, and Affiliated Hospital, Guangdong Medical University, Shenzhen, Guangdong, China.

Insights

Programmed cell death protein 1 (PD-1)-expressing mucosal-associated invariant T (MAIT) cells in human tuberculosis produce CXCL13 and IL-21. These cells show altered function and increased presence in pleural tuberculosis infections.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Cellular Biology

Background:

  • Mucosal-associated invariant T (MAIT) cells play a role in host defense against infections.
  • Programmed cell death protein 1 (PD-1) is an inhibitory receptor expressed on immune cells.
  • The function of PD-1-expressing MAIT cells during tuberculosis (TB) infection is not well understood.

Purpose of the Study:

  • To elucidate the functional role of PD-1-expressing MAIT cells in human tuberculosis.
  • To characterize the phenotype and function of PD-1+ MAIT cells in the context of TB.

Main Methods:

  • Sorted PD-1+ and PD-1- MAIT cells from pleural effusions of patients with pleural tuberculosis.
  • Transcriptome sequencing to identify differentially expressed genes.
  • Flow cytometry to analyze phenotypic and functional features, including cytokine production, cell surface markers, glucose uptake, and lipid content.

Main Results:

  • Transcriptome sequencing revealed 144 differentially expressed genes between PD-1+ and PD-1- MAIT cells, with CXCL13 showing the highest fold difference.
  • The level of PD-1-expressing MAIT cells correlated with the extent of TB infection.
  • PD-1+ MAIT cells exhibited increased production of CXCL13 and IL-21.
  • PD-1high CXCR5- MAIT cells were expanded in pleural effusions compared to peripheral blood.
  • These expanded cells showed reduced IFN-γ but increased Tim-3 and GITR expression, alongside an activated phenotype with higher glucose uptake and lipid content.

Conclusions:

  • PD-1-expressing MAIT cells in human tuberculosis exhibit a distinct functional profile.
  • These cells are characterized by reduced IFN-γ production but increased CXCL13 and IL-21 secretion.
  • The findings suggest a complex role for PD-1+ MAIT cells in the immune response to tuberculosis.