TY - JOUR
T1 - Blockade effects of anti-interferon- (ifn-) γ autoantibodies on ifn- γ -regulated antimicrobial immunity
AU - Krisnawati, Dyah Ika
AU - Liu, Yung Ching
AU - Lee, Yuarn Jang
AU - Wang, Yun Ting
AU - Chen, Chia Ling
AU - Tseng, Po Chun
AU - Shen, Ting Jing
AU - Lin, Chiou Feng
N1 - Funding Information:
We gratefully acknowledge the financial support from the Ministry of Research, Technology and Higher Education of the Republic of Indonesia (3273/E4.4/K/2014) for Dyah Ika Krisnawati. We also thank the Core Facility Center of Taipei Medical University (TMU) for providing technical support. This study is supported by grants from the Ministry of Science and Technology (MOST102-2628-B-038-011-MY3 and 107-2320-B-038-063), Taipei, Taiwan.
Publisher Copyright:
© 2019 Dyah Ika Krisnawati et al.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - The interferon- (IFN-) γ expression is elicited in response to microbial infections and activates immune surveillance by antimicrobial immune elements to induce microbial killing. Patients with adult-onset immunodeficiency who suffer from recurrent infections with microbes, particularly nontuberculous mycobacteria (NTM), commonly display genetic defects in IFN-γ signaling as well as the generation of anti-IFN-γ autoantibodies (autoAbs). Because IFN-γ is an activator of macrophage differentiation and a proinflammatory activator of innate immunity, the blockade effects of the autoAbs present in NTM patient serum on IFN-γ are hypothesized to regulate the antimicrobial function of macrophages. In the presence of patient serum, IFN-γ-induced type 1 macrophage (M1) differentiation was inhibited in PMA-stimulated human monocytic THP-1 cells. Treatment with patient serum significantly blocked the production of proinflammatory factors, including cytokines/chemokines and reactive oxygen/nitrogen species, by M1 macrophages. Importantly, IFN-γ-facilitated phagocytosis and degradation of heat-killed mycobacterium were decreased by cotreatment with patient serum. These results show the blockade activity of anti-IFN-γ autoAbs on IFN-γ-mediated antimicrobial immunity in macrophages.
AB - The interferon- (IFN-) γ expression is elicited in response to microbial infections and activates immune surveillance by antimicrobial immune elements to induce microbial killing. Patients with adult-onset immunodeficiency who suffer from recurrent infections with microbes, particularly nontuberculous mycobacteria (NTM), commonly display genetic defects in IFN-γ signaling as well as the generation of anti-IFN-γ autoantibodies (autoAbs). Because IFN-γ is an activator of macrophage differentiation and a proinflammatory activator of innate immunity, the blockade effects of the autoAbs present in NTM patient serum on IFN-γ are hypothesized to regulate the antimicrobial function of macrophages. In the presence of patient serum, IFN-γ-induced type 1 macrophage (M1) differentiation was inhibited in PMA-stimulated human monocytic THP-1 cells. Treatment with patient serum significantly blocked the production of proinflammatory factors, including cytokines/chemokines and reactive oxygen/nitrogen species, by M1 macrophages. Importantly, IFN-γ-facilitated phagocytosis and degradation of heat-killed mycobacterium were decreased by cotreatment with patient serum. These results show the blockade activity of anti-IFN-γ autoAbs on IFN-γ-mediated antimicrobial immunity in macrophages.
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U2 - 10.1155/2019/1629258
DO - 10.1155/2019/1629258
M3 - Article
C2 - 31275997
AN - SCOPUS:85067125353
SN - 2314-8861
VL - 2019
JO - Journal of Immunology Research
JF - Journal of Immunology Research
M1 - 1629258
ER -