Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment
Uloženo v:
| Název: | Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment |
|---|---|
| Autoři: | Caleb Nwongbouwoh Muefong, Abhishek Bakuli, Simon Donkor, Salome Charalambous, Andrea Rachow, Olumuyiwa Owolabi, Christof Geldmacher, Jayne S. Sutherland |
| Zdroj: | Clin Infect Dis |
| Informace o vydavateli: | Oxford University Press (OUP), 2021. |
| Rok vydání: | 2021 |
| Témata: | 0301 basic medicine, Major Articles and Commentaries, Antigens, Bacterial, 0303 health sciences, 03 medical and health sciences, Neutrophils, Humans, Tuberculosis, Mycobacterium tuberculosis, Reactive Oxygen Species, Lung, Interleukin-10, 3. Good health |
| Popis: | Background Despite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung recovery. Neutrophils are associated with lung pathology; however, CD16/CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype, and function of neutrophils following stimulation with Mycobacterium tuberculosis (Mtb) whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC) in relation to lung pathology. Methods Fresh blood from 42 adult, human immunodeficiency virus (HIV)–negative TB patients were analyzed pre- and post-therapy, with disease severity determined using chest radiography and bacterial load. Flow cytometry was used to monitor frequencies, phenotype, and function (generation of reactive oxygen species [ROS], together with CD11b, tumor necrosis factor, and interleukin 10 [IL-10] expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens. Results Total neutrophils decreased by post-treatment compared to baseline (P = .0059); however, CD16brCD62Lbr (segmented) neutrophils increased (P = .0031) and CD16dimCD62Lbr (banded) neutrophils decreased (P = .038). Banded neutrophils were lower in patients with severe lung damage at baseline (P = .035). Following WCL stimulation, ROS from segmented neutrophils was higher in patients with low Mtb loads even after adjusting for sex (P = .038), whereas IL-10–expressing CD16dimCD62Llo cells were higher in patients with mild damage (P = .0397) at baseline. Conclusions High ROS generation, low levels of banded neutrophils, and high levels of IL-10–expressing CD16dimCD62Llo neutrophils are associated with reduced lung pathology at diagnosis. Hence, neutrophils are potential early indicators of TB severity and promising targets for TB host-directed therapy. |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1537-6591 1058-4838 |
| DOI: | 10.1093/cid/ciab729 |
| Přístupová URL adresa: | https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciab729/40833861/ciab729.pdf https://pubmed.ncbi.nlm.nih.gov/34427644 https://researchonline.lshtm.ac.uk/id/eprint/4663322/1/ciab729.pdf https://pubmed.ncbi.nlm.nih.gov/34427644/ |
| Rights: | CC BY NC ND CC BY |
| Přístupové číslo: | edsair.doi.dedup.....9ee6cdb94a15f491889f05ed12835034 |
| Databáze: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstrakt: | Background Despite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung recovery. Neutrophils are associated with lung pathology; however, CD16/CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype, and function of neutrophils following stimulation with Mycobacterium tuberculosis (Mtb) whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC) in relation to lung pathology. Methods Fresh blood from 42 adult, human immunodeficiency virus (HIV)–negative TB patients were analyzed pre- and post-therapy, with disease severity determined using chest radiography and bacterial load. Flow cytometry was used to monitor frequencies, phenotype, and function (generation of reactive oxygen species [ROS], together with CD11b, tumor necrosis factor, and interleukin 10 [IL-10] expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens. Results Total neutrophils decreased by post-treatment compared to baseline (P = .0059); however, CD16brCD62Lbr (segmented) neutrophils increased (P = .0031) and CD16dimCD62Lbr (banded) neutrophils decreased (P = .038). Banded neutrophils were lower in patients with severe lung damage at baseline (P = .035). Following WCL stimulation, ROS from segmented neutrophils was higher in patients with low Mtb loads even after adjusting for sex (P = .038), whereas IL-10–expressing CD16dimCD62Llo cells were higher in patients with mild damage (P = .0397) at baseline. Conclusions High ROS generation, low levels of banded neutrophils, and high levels of IL-10–expressing CD16dimCD62Llo neutrophils are associated with reduced lung pathology at diagnosis. Hence, neutrophils are potential early indicators of TB severity and promising targets for TB host-directed therapy. |
|---|---|
| ISSN: | 15376591 10584838 |
| DOI: | 10.1093/cid/ciab729 |