Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients

Author:

Dai Youchao1,Cai Yi2,Wang Xin3,Zhu Jialou2,Liu Xiaoqian45,Liu Houming6,Li Linghua1,Zhang Yinze3,Liu Shengze7,Wen Zhihua7,Feng Carl G.8,Chen Xinchun2,Tang Xiaoping1

Affiliation:

1. Research Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, China

2. Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China

3. International Cancer Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China

4. Department of Infectious Disease, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China

5. Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong Province, China

6. Clinical Laboratory, Shenzhen Third People’s Hospital, Shenzhen University School of Medicine, Shenzhen, China

7. Yuebei Second People’s Hospital, Shaoguan, China

8. Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia

Abstract

HIV infection significantly increases TB susceptibility due to CD4 T-cell loss and macrophage dysfunction. Although it is relatively clear that CD4 T-cell loss represents a direct effect of HIV infection, the mechanism underlying how HIV infection dampens macrophage function is unknown. Here, we show that HIV infection enhances autoantibody-mediated erythrophagocytosis, which dampens macrophage bactericidal activity against TB by inhibiting HO-1-associated autophagy. Our findings reveal a novel mechanism explaining how HIV infection increases susceptibility to TB. We propose that DAT could be a potential measure to identify HIV patients who are at high TB risk and who would be suitable for anti-TB chemotherapy preventive treatment.

Funder

Science and Technology Project of Shenzhen

Natural Science Foundation of China

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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