Chin-Chung Shu1, Jann-Yuan Wang1, Ming-Fang Wu2, Hsin-Chih Lai3, Bor-Luen Chiang4, Chong-Jen Yu5. 1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC. 2. Institute of Biomedical Sciences, Academia Sinica,Taipei, Taiwan, ROC; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC. 3. Department of Medical Biotechnology and Laboratory Science, Microbiota Research Center, Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, An College of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan, ROC; Department of Laboratory Medicine and Chang Gung Immunology Consortium, Chang Gung Memorial hospital, Tao-Yuan, Taiwan, ROC. 4. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC. 5. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: jefferycjyu@ntu.edu.tw.
Abstract
BACKGROUND: Mycobacterium avium complex (MAC)-lung disease (LD) is increasing in patients without human immunodeficiency virus infection. However, data on host vulnerability to MAC-related immune responses, and in particular the interleukin (IL)-23/IL-17 axis, are lacking. METHODS: We enrolled 50 patients with MAC-LD, 25 age-matched patients with tuberculosis (TB) and 25 controls. We measured levels of plasma cytokines, and studied IL-12/IL-17 responses in macrophage and lymphocyte activation to MAC. RESULTS: The plasma level of IL-17 in the MAC group was higher than in the TB and control groups. In in-vitro macrophage stimulation, the expression of IL-23 in macrophages was similar in the patients with MAC-LD and controls, although the expression of IL-12 p40 was lower in the patients with MAC-LD. In assays of lymphocyte activation, IL-17 was induced by MAC-primed macrophages, but its level was lower in the patients with MAC-LD and TB than in the controls. The expression of programmed death (PD)-1 receptor was higher in CD4+IL17A+ lymphocytes in the patients with MAC-LD, and the production of IL-17 was significantly increased by blockade of PD-1 and PD-ligand 1. CONCLUSIONS: MAC induced a similar expression of IL-23 from macrophages in the patients with MAC-LD compared to the controls, but a lower expression of IL-17 from lymphocytes, which may be through an increased expression of PD-1. The macrophage response of IL-12 p40 was stronger than that of IL-12 p70, and higher in the controls during MAC disease, which may suggest another kind of MAC-related immune evasion.
BACKGROUND:Mycobacterium avium complex (MAC)-lung disease (LD) is increasing in patients without human immunodeficiency virus infection. However, data on host vulnerability to MAC-related immune responses, and in particular the interleukin (IL)-23/IL-17 axis, are lacking. METHODS: We enrolled 50 patients with MAC-LD, 25 age-matched patients with tuberculosis (TB) and 25 controls. We measured levels of plasma cytokines, and studied IL-12/IL-17 responses in macrophage and lymphocyte activation to MAC. RESULTS: The plasma level of IL-17 in the MAC group was higher than in the TB and control groups. In in-vitro macrophage stimulation, the expression of IL-23 in macrophages was similar in the patients with MAC-LD and controls, although the expression of IL-12 p40 was lower in the patients with MAC-LD. In assays of lymphocyte activation, IL-17 was induced by MAC-primed macrophages, but its level was lower in the patients with MAC-LD and TB than in the controls. The expression of programmed death (PD)-1 receptor was higher in CD4+IL17A+ lymphocytes in the patients with MAC-LD, and the production of IL-17 was significantly increased by blockade of PD-1 and PD-ligand 1. CONCLUSIONS:MAC induced a similar expression of IL-23 from macrophages in the patients with MAC-LD compared to the controls, but a lower expression of IL-17 from lymphocytes, which may be through an increased expression of PD-1. The macrophage response of IL-12 p40 was stronger than that of IL-12 p70, and higher in the controls during MAC disease, which may suggest another kind of MAC-related immune evasion.
Authors: Milou M F Schuurbiers; Mariolina Bruno; Sanne M H Zweijpfenning; Cecile Magis-Escurra; Martin Boeree; Mihai G Netea; Jakko van Ingen; Frank van de Veerdonk; Wouter Hoefsloot Journal: ERJ Open Res Date: 2020-11-10