Identification of circulating monocytes as producers of tuberculosis disease biomarker C1q

Paula Niewold; Douwe J Dijkstra; Yi Cai; Delia Goletti; Fabrizio Palmieri; Krista E van Meijgaarden; Frank A W Verreck; Onno W Akkerman; Regina W Hofland; Eveline M Delemarre; Stefan Nierkens; Marije K Verheul; Andrew J Pollard; Jaap T van Dissel; Tom H M Ottenhoff; Leendert A Trouw; Simone A Joosten

doi:10.1038/s41598-023-38889-x

Identification of circulating monocytes as producers of tuberculosis disease biomarker C1q

Paula Niewold, Douwe J Dijkstra, Yi Cai, Delia Goletti, Fabrizio Palmieri, Krista E van Meijgaarden, Frank A W Verreck, Onno W Akkerman, Regina W Hofland, Eveline M Delemarre, Stefan Nierkens, Marije K Verheul, Andrew J Pollard, Jaap T van Dissel, Tom H M Ottenhoff, Leendert A Trouw, Simone A Joosten

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Abstract

Tuberculosis (TB) is a prevalent disease causing an estimated 1.6 million deaths and 10.6 million new cases annually. Discriminating TB disease from differential diagnoses can be complex, particularly in the field. Increased levels of complement component C1q in serum have been identified as a specific and accessible biomarker for TB disease but the source of C1q in circulation has not been identified. Here, data and samples previously collected from human cohorts, a clinical trial and a non-human primate study were used to identify cells producing C1q in circulation. Cell subset frequencies were correlated with serum C1q levels and combined with single cell RNA sequencing and flow cytometry analyses. This identified monocytes as C1q producers in circulation, with a pronounced expression of C1q in classical and intermediate monocytes and variable expression in non-classical monocytes.

Original language	English
Article number	11617
Pages (from-to)	1-10
Journal	Scientific Reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-023-38889-x
Publication status	Published - 18 Jul 2023

Keywords

Animals
Biomarkers/metabolism
Complement C1q/metabolism
Humans
Monocytes/metabolism
Primates
Tuberculosis/diagnosis

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Niewold, P., Dijkstra, D. J., Cai, Y., Goletti, D., Palmieri, F., van Meijgaarden, K. E., Verreck, F. A. W., Akkerman, O. W., Hofland, R. W., Delemarre, E. M., Nierkens, S., Verheul, M. K., Pollard, A. J., van Dissel, J. T., Ottenhoff, T. H. M., Trouw, L. A., & Joosten, S. A. (2023). Identification of circulating monocytes as producers of tuberculosis disease biomarker C1q. Scientific Reports, 13(1), 1-10. Article 11617. https://doi.org/10.1038/s41598-023-38889-x

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title = "Identification of circulating monocytes as producers of tuberculosis disease biomarker C1q",

abstract = "Tuberculosis (TB) is a prevalent disease causing an estimated 1.6 million deaths and 10.6 million new cases annually. Discriminating TB disease from differential diagnoses can be complex, particularly in the field. Increased levels of complement component C1q in serum have been identified as a specific and accessible biomarker for TB disease but the source of C1q in circulation has not been identified. Here, data and samples previously collected from human cohorts, a clinical trial and a non-human primate study were used to identify cells producing C1q in circulation. Cell subset frequencies were correlated with serum C1q levels and combined with single cell RNA sequencing and flow cytometry analyses. This identified monocytes as C1q producers in circulation, with a pronounced expression of C1q in classical and intermediate monocytes and variable expression in non-classical monocytes.",

keywords = "Animals, Biomarkers/metabolism, Complement C1q/metabolism, Humans, Monocytes/metabolism, Primates, Tuberculosis/diagnosis",

author = "Paula Niewold and Dijkstra, {Douwe J} and Yi Cai and Delia Goletti and Fabrizio Palmieri and {van Meijgaarden}, {Krista E} and Verreck, {Frank A W} and Akkerman, {Onno W} and Hofland, {Regina W} and Delemarre, {Eveline M} and Stefan Nierkens and Verheul, {Marije K} and Pollard, {Andrew J} and {van Dissel}, {Jaap T} and Ottenhoff, {Tom H M} and Trouw, {Leendert A} and Joosten, {Simone A}",

note = "Funding Information: This work was partially supported by the following grants: National Institute for Infectious Diseases-IRCCS L. Spallanzani, Rome, Italy; Line 4 four-Ricerca Corrente, funded by the Italian Ministry of Health; European Union EC HORIZON2020 TBVAC2020 (Grant Agreement No. 643381); UK Medical Research Council (MRC) (MR/K021222/1) and the Oxford Biomedical Research Centre. The funders were not involved in the study design, collection, analysis, and interpretation of data, writing of this article, or the decision to submit it for publication. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = jul,

day = "18",

doi = "10.1038/s41598-023-38889-x",

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Niewold, P, Dijkstra, DJ, Cai, Y, Goletti, D, Palmieri, F, van Meijgaarden, KE, Verreck, FAW, Akkerman, OW, Hofland, RW, Delemarre, EM, Nierkens, S, Verheul, MK, Pollard, AJ, van Dissel, JT, Ottenhoff, THM, Trouw, LA & Joosten, SA 2023, 'Identification of circulating monocytes as producers of tuberculosis disease biomarker C1q', Scientific Reports, vol. 13, no. 1, 11617, pp. 1-10. https://doi.org/10.1038/s41598-023-38889-x

TY - JOUR

T1 - Identification of circulating monocytes as producers of tuberculosis disease biomarker C1q

AU - Niewold, Paula

AU - Dijkstra, Douwe J

AU - Cai, Yi

AU - Goletti, Delia

AU - Palmieri, Fabrizio

AU - van Meijgaarden, Krista E

AU - Verreck, Frank A W

AU - Akkerman, Onno W

AU - Hofland, Regina W

AU - Delemarre, Eveline M

AU - Nierkens, Stefan

AU - Verheul, Marije K

AU - Pollard, Andrew J

AU - van Dissel, Jaap T

AU - Ottenhoff, Tom H M

AU - Trouw, Leendert A

AU - Joosten, Simone A

N1 - Funding Information: This work was partially supported by the following grants: National Institute for Infectious Diseases-IRCCS L. Spallanzani, Rome, Italy; Line 4 four-Ricerca Corrente, funded by the Italian Ministry of Health; European Union EC HORIZON2020 TBVAC2020 (Grant Agreement No. 643381); UK Medical Research Council (MRC) (MR/K021222/1) and the Oxford Biomedical Research Centre. The funders were not involved in the study design, collection, analysis, and interpretation of data, writing of this article, or the decision to submit it for publication. Publisher Copyright: © 2023, The Author(s).

PY - 2023/7/18

Y1 - 2023/7/18

N2 - Tuberculosis (TB) is a prevalent disease causing an estimated 1.6 million deaths and 10.6 million new cases annually. Discriminating TB disease from differential diagnoses can be complex, particularly in the field. Increased levels of complement component C1q in serum have been identified as a specific and accessible biomarker for TB disease but the source of C1q in circulation has not been identified. Here, data and samples previously collected from human cohorts, a clinical trial and a non-human primate study were used to identify cells producing C1q in circulation. Cell subset frequencies were correlated with serum C1q levels and combined with single cell RNA sequencing and flow cytometry analyses. This identified monocytes as C1q producers in circulation, with a pronounced expression of C1q in classical and intermediate monocytes and variable expression in non-classical monocytes.

AB - Tuberculosis (TB) is a prevalent disease causing an estimated 1.6 million deaths and 10.6 million new cases annually. Discriminating TB disease from differential diagnoses can be complex, particularly in the field. Increased levels of complement component C1q in serum have been identified as a specific and accessible biomarker for TB disease but the source of C1q in circulation has not been identified. Here, data and samples previously collected from human cohorts, a clinical trial and a non-human primate study were used to identify cells producing C1q in circulation. Cell subset frequencies were correlated with serum C1q levels and combined with single cell RNA sequencing and flow cytometry analyses. This identified monocytes as C1q producers in circulation, with a pronounced expression of C1q in classical and intermediate monocytes and variable expression in non-classical monocytes.

KW - Animals

KW - Biomarkers/metabolism

KW - Complement C1q/metabolism

KW - Humans

KW - Monocytes/metabolism

KW - Primates

KW - Tuberculosis/diagnosis

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U2 - 10.1038/s41598-023-38889-x

DO - 10.1038/s41598-023-38889-x

M3 - Article

C2 - 37464009

SN - 2045-2322

VL - 13

SP - 1

EP - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 11617

ER -

Identification of circulating monocytes as producers of tuberculosis disease biomarker C1q

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