دورية أكاديمية
Regulation of mycobacterial infection by macrophage Gch1 and tetrahydrobiopterin
| العنوان: | Regulation of mycobacterial infection by macrophage Gch1 and tetrahydrobiopterin |
|---|---|
| المؤلفون: | McNeill, E, Stylianou, E, Crabtree, M, Harrington-Kandt, RL, Kolb, AL, Diotallevi, M, Hale, A, Bettencourt, PJG, Tanner, R, O'Shea, M, Matsumiya, M, Lockstone, H, Muller, J, Fletcher, H, Greaves, D, McShane, H, Channon, K |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2018 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | Inducible nitric oxide synthase (iNOS) plays a crucial role in controlling growth of Mycobacterium tuberculosis (M.tb), presumably via nitric oxide (NO) mediated killing. Here we show that leukocyte-specific deficiency of NO production, through targeted loss of the iNOS cofactor tetrahydrobiopterin (BH4), results in enhanced control of M.tb infection; by contrast, loss of iNOS renders mice susceptible to M.tb. By comparing two complementary NO-deficient models, Nos2-/-mice and BH4 deficient Gch1fl/fl Tie2cre mice, we uncover NO-independent mechanisms of anti-mycobacterial immunity. In both 38 murine and human leukocytes, decreased Gch1 expression correlates with enhanced cell intrinsic control of mycobacterial infection in vitro. Gene expression analysis reveals that Gch1 deficient macrophages have altered inflammatory response, lysosomal function, cell survival and cellular metabolism, thereby dampening the control of bacterial infection. Our data thus highlight the importance of the NO-independent functions of Nos2 and Gch1 in mycobacterial control. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://ora.ox.ac.uk/objects/uuid:f1bb7a8b-4b81-4223-bf96-14413e1080beTest; https://doi.org/10.1038/s41467-018-07714-9Test |
| DOI: | 10.1038/s41467-018-07714-9 |
| الإتاحة: | https://doi.org/10.1038/s41467-018-07714-9Test https://ora.ox.ac.uk/objects/uuid:f1bb7a8b-4b81-4223-bf96-14413e1080beTest |
| حقوق: | info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| رقم الانضمام: | edsbas.A8876EBF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-018-07714-9 |
|---|