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Publications

Journal Article Epublish

PubMed: 38745652 DOI: 10.3389/fimmu.2024.1360412

Myeloid cell expression of CD200R is modulated in active TB disease and regulates infection in a biomimetic model.

Front Immunol 15:1360412

Authors: Mohamed Ahmed, Liku B Tezera, Nicholas Herbert, Mark Chambers, Michaela T Reichmann, Kievershen Nargan, Henrik Kloverpris, Farina Karim, Mbali Hlatshwayo, Rajhmun Madensein, Munir Habesh, Monjural Hoque, Adrie J C Steyn, Paul T Elkington, Alasdair J Leslie

Affiliations

  • Africa Health Research Institute, Durban, South Africa. College of Health Sciences, School of Laboratory Medicine & Medical Sciences, University of KwaZulu Natal, Durban, South Africa.
  • NIHR Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
  • Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
  • Africa Health Research Institute, Durban, South Africa.
  • College of Health Sciences, School of Laboratory Medicine & Medical Sciences, University of KwaZulu Natal, Durban, South Africa.
  • Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
  • Department of Infection and Immunity, University College London, London, United Kingdom.
  • Department of Cardiothoracic Surgery, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
  • Kwadabeka Community Health Care Centre, Kwadabeka, South Africa.
  • Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States.

Abstract

A robust immune response is required for resistance to pulmonary tuberculosis (TB), the primary disease caused by (). However, pharmaceutical inhibition of T cell immune checkpoint molecules can result in the rapid development of active disease in latently infected individuals, indicating the importance of T cell immune regulation. In this study, we investigated the potential role of CD200R during infection, a key immune checkpoint for myeloid cells. Expression of CD200R was consistently downregulated on CD14 monocytes in the blood of subjects with active TB compared to healthy controls, suggesting potential modulation of this important anti-inflammatory pathway. In homogenized TB-diseased lung tissue, CD200R expression was highly variable on monocytes and CD11bHLA-DR macrophages but tended to be lowest in the most diseased lung tissue sections. This observation was confirmed by fluorescent microscopy, which showed the expression of CD200R on CD68 macrophages surrounding TB lung granuloma and found expression levels tended to be lower in macrophages closest to the granuloma core and inversely correlated with lesion size. Antibody blockade of CD200R in a biomimetic 3D granuloma-like tissue culture system led to significantly increased growth. In addition, infection in this system reduced gene expression of CD200R. These findings indicate that regulation of myeloid cells via CD200R is likely to play an important part in the immune response to TB and may represent a potential target for novel therapeutic intervention.

MeSH

Granuloma, Lung, Monocytes, Biomimetics, Macrophages, Immune System Diseases, Myeloid Cells, Tuberculosis, Immunity, Innate, Tissues, T-Lymphocytes, Infections