Antibody-Mediated LILRB2-Receptor Antagonism Induces Human Myeloid-Derived Suppressor Cells to Kill Mycobacterium tuberculosis

Vipul K. Singh, Arshad Khan, Yitian Xu, Sunny Mai, Licheng Zhang, Abhishek Mishra, Blanca I. Restrepo, Ping Ying Pan, Shu Hsia Chen, Chinnaswamy Jagannath

Research output: Contribution to journalArticlepeer-review

Abstract

Tuberculosis is a leading cause of death in mankind due to infectious agents, and Mycobacterium tuberculosis (Mtb) infects and survives in macrophages (MФs). Although MФs are a major niche, myeloid-derived suppressor cells (MDSCs) are an alternative site for pathogen persistence. Both MФs and MDSCs express varying levels of leukocyte immunoglobulin-like receptor B (LILRB), which regulate the myeloid cell suppressive function. Herein, we demonstrate that antagonism of LILRB2 by a monoclonal antibody (mab) induced a switch of human MDSCs towards an M1-macrophage phenotype, increasing the killing of intracellular Mtb. Mab-mediated antagonism of LILRB2 alone and its combination with a pharmacological blockade of SHP1/2 phosphatase increased proinflammatory cytokine responses and phosphorylation of ERK1/2, p38 MAPK, and NF-kB in Mtb-infected MDSCs. LILRB2 antagonism also upregulated anti-mycobacterial iNOS gene expression and an increase in both nitric oxide and reactive oxygen species synthesis. Because genes associated with the anti-mycobacterial function of M1-MФs were enhanced in MDSCs following mab treatment, we propose that LILRB2 antagonism reprograms MDSCs from an immunosuppressive state towards a pro-inflammatory phenotype that kills Mtb. LILRB2 is therefore a novel therapeutic target for eradicating Mtb in MDSCs.

Original languageEnglish (US)
Article number865503
JournalFrontiers in immunology
Volume13
DOIs
StatePublished - Jun 10 2022

Keywords

  • LILRB
  • MDSC (myeloid-derived suppressor cell)
  • Mycobacterium
  • monoclonal antibody
  • tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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