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Emerg Microbes Infect. 2018 Dec 12;7(1):207. doi: 10.1038/s41426-018-0213-z.

Multidrug-resistant tuberculosis (MDR-TB) strain infection in macaques results in high bacilli burdens in airways, driving broad innate/adaptive immune responses.

Author information

1
Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
2
Department of Microbiology & Immunology and Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL, USA.
3
Unit of Anti-Tuberculosis Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
4
College of Medicine,Wuhan University, Wuhan, Hubei Province, 430072, China.
5
Department of Medical Microbiology and Parasitology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
6
Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. xiaoheping_sars@163.com.
7
Department of Microbiology & Immunology and Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL, USA. zchen@uic.edu.
8
Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. hongboshen109@hotmail.com.
9
Unit of Anti-Tuberculosis Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. hongboshen109@hotmail.com.

Abstract

Tuberculosis (TB) has become the most deadly infectious diseases due to epidemics of HIV/AIDS and multidrug-resistant/extensively drug-resistant TB (MDR-/XDR-TB). Although person-to-person transmission contributes to MDR-TB, it remains unknown whether infection with MDR strains resembles infection with drug-sensitive (DS) TB strains, manipulating limited or broad immune responses. To address these questions, macaques were infected with MDR strain V791 and a drug-sensitive Erdman strain of TB. MDR bacilli burdens in the airway were significantly higher than those of the Erdman control after pulmonary exposure. This productive MDR strain infection upregulated the expression of caspase 3 in macrophages/monocytes and induced appreciable innate-like effector responses of CD3-negative lymphocytes and Ag-specific γδ T-cell subsets. Concurrently, MDR strain infection induced broad immune responses of T-cell subpopulations producing Th1, Th17, Th22, and CTL cytokines. Furthermore, MDR bacilli, like the Erdman strain, were capable of inducing typical TB disease characterized by weight loss, lymphocytopenia, and severe TB lesions. For the first time, our results suggest that MDR-TB infection acts like DS to induce high bacterial burdens in the airway (transmission advantage), innate/adaptive immune responses, and disease processes. Because nonhuman primates are biologically closer to humans than other species, our data may provide useful information for predicting the effects of primary MDR strain infection after person-to-person transmission. The findings also support the hypothesis that a vaccine or host-directed adjunctive modality that is effective for drug-sensitive TB is likely to also impact MDR-TB.

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