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

Myeloid cell expression of CD200R is modulated in active TB disease and regulates Mycobacterium tuberculosis infection in a biomimetic model
Myeloid cell expression of CD200R is modulated in active TB disease and regulates Mycobacterium tuberculosis infection in a biomimetic model
A robust immune response is required for resistance to pulmonary tuberculosis (TB), the primary disease caused by Mycobacterium tuberculosis (Mtb). 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 Mtb 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 CD11b + HLA-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 Mtb growth. In addition, Mtb 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.
Adult, Antigens, CD/metabolism, Biomimetics, Female, Humans, Lung/immunology, Macrophages/immunology, Male, Middle Aged, Monocytes/immunology, Mycobacterium tuberculosis/immunology, Myeloid Cells/immunology, Orexin Receptors/metabolism, Tuberculosis, Pulmonary/immunology, Tuberculosis, pulmonary infection, Immune checkpoint, CD200 receptor, innate immunity, CD200 receptor, tuberculosis, pulmonary infection, innate immunity, immune checkpoint
1664-3224
1360412
Ahmed, Mohamed
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Tezera, Liku B.
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Herbert, Nicholas G.
f91adb39-acba-4edc-abe5-26155854f36a
Chambers, Mark
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Reichmann, Michaela
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Nargan, Kievershen
dcf2a186-1504-4422-a748-798f17aa01fd
Kløverpris, Henrik N.
a91c6912-f59e-4766-be0f-c553af752929
Karim, Farina
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Hlatshwayo, Mbali
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Madensein, Rajhmun
8d7da91a-63fa-434d-82f4-f53b9e3a566a
Habesh, Munir
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Hoque, Monjural
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Steyn, Adrie J.
22ae8166-ffea-472f-8e8c-be3be05bdce2
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Leslie, Alasdair
00f79867-4024-4596-80b6-bc279515da01
Ahmed, Mohamed
9d82d448-7f08-4304-a5d2-b8cf12317353
Tezera, Liku B.
c5598dbf-23a8-4934-96a4-7c783bf9e776
Herbert, Nicholas G.
f91adb39-acba-4edc-abe5-26155854f36a
Chambers, Mark
5a7a425f-171a-467a-8c04-c95e64bfba8e
Reichmann, Michaela
d887f227-13a8-4384-a1c5-d3c229cd0642
Nargan, Kievershen
dcf2a186-1504-4422-a748-798f17aa01fd
Kløverpris, Henrik N.
a91c6912-f59e-4766-be0f-c553af752929
Karim, Farina
15c7107f-022a-44f3-bcfc-b56746587dda
Hlatshwayo, Mbali
612c2441-db93-4d21-9d4a-80d08191730f
Madensein, Rajhmun
8d7da91a-63fa-434d-82f4-f53b9e3a566a
Habesh, Munir
1ea7a905-5210-421f-9cef-de877b891bd5
Hoque, Monjural
baa694f6-d58c-4c2c-8305-950fa0a8fb49
Steyn, Adrie J.
22ae8166-ffea-472f-8e8c-be3be05bdce2
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Leslie, Alasdair
00f79867-4024-4596-80b6-bc279515da01

Ahmed, Mohamed, Tezera, Liku B., Herbert, Nicholas G., Chambers, Mark, Reichmann, Michaela, Nargan, Kievershen, Kløverpris, Henrik N., Karim, Farina, Hlatshwayo, Mbali, Madensein, Rajhmun, Habesh, Munir, Hoque, Monjural, Steyn, Adrie J., Elkington, Paul and Leslie, Alasdair (2024) Myeloid cell expression of CD200R is modulated in active TB disease and regulates Mycobacterium tuberculosis infection in a biomimetic model. Frontiers in Immunology, 15, 1360412, [1360412]. (doi:10.3389/fimmu.2024.1360412).

Record type: Article

Abstract

A robust immune response is required for resistance to pulmonary tuberculosis (TB), the primary disease caused by Mycobacterium tuberculosis (Mtb). 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 Mtb 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 CD11b + HLA-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 Mtb growth. In addition, Mtb 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.

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CD200R modulates immune control of human tuberculosis_final2 - Accepted Manuscript
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Accepted/In Press date: 26 March 2024
Published date: 2024
Additional Information: Publisher Copyright: Copyright © 2024 Ahmed, Tezera, Herbert, Chambers, Reichmann, Nargan, Kloverpris, Karim, Hlatshwayo, Madensein, Habesh, Hoque, Steyn, Elkington and Leslie.
Keywords: Adult, Antigens, CD/metabolism, Biomimetics, Female, Humans, Lung/immunology, Macrophages/immunology, Male, Middle Aged, Monocytes/immunology, Mycobacterium tuberculosis/immunology, Myeloid Cells/immunology, Orexin Receptors/metabolism, Tuberculosis, Pulmonary/immunology, Tuberculosis, pulmonary infection, Immune checkpoint, CD200 receptor, innate immunity, CD200 receptor, tuberculosis, pulmonary infection, innate immunity, immune checkpoint

Identifiers

Local EPrints ID: 489298
URI: http://eprints.soton.ac.uk/id/eprint/489298
ISSN: 1664-3224
PURE UUID: ebfe2a3c-b465-49d6-8ca6-305ab7f912f0
ORCID for Liku B. Tezera: ORCID iD orcid.org/0000-0002-7898-6709
ORCID for Michaela Reichmann: ORCID iD orcid.org/0000-0002-3015-9827
ORCID for Paul Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 19 Apr 2024 16:39
Last modified: 01 Oct 2024 04:04

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Contributors

Author: Mohamed Ahmed
Author: Liku B. Tezera ORCID iD
Author: Nicholas G. Herbert
Author: Mark Chambers
Author: Michaela Reichmann ORCID iD
Author: Kievershen Nargan
Author: Henrik N. Kløverpris
Author: Farina Karim
Author: Mbali Hlatshwayo
Author: Rajhmun Madensein
Author: Munir Habesh
Author: Monjural Hoque
Author: Adrie J. Steyn
Author: Paul Elkington ORCID iD
Author: Alasdair Leslie

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