Multidrug-resistant tuberculosis (MDR-TB) strain infection in macaques results in high bacilli burdens in airways, driving broad innate/adaptive immune responses
| Autor: | Zhuoran Zhang, Hongbo Shen, Crystal Y. Chen, Ming Guo, Enzhuo Yang, Wenzhe Ho, Heping Xiao, Rui Yang, Wandang Wang, Dan Huang, Zheng W. Chen, Ling Shen, Feifei Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tuberculosis Epidemiology Immunology lcsh:QR1-502 Drug resistance Adaptive Immunity Biology Microbiology Article lcsh:Microbiology lcsh:Infectious and parasitic diseases 03 medical and health sciences Th2 Cells Immune system Immunity Drug Resistance Multiple Bacterial Virology Tuberculosis Multidrug-Resistant Drug Discovery medicine Animals lcsh:RC109-216 Lung Tuberculosis Pulmonary Caspase 3 Transmission (medicine) Macrophages General Medicine Th1 Cells Acquired immune system medicine.disease Bacterial Load Immunity Innate 3. Good health Multiple drug resistance 030104 developmental biology Infectious Diseases Cytokines Macaca Th17 Cells Parasitology Lymphocytopenia |
| Zdroj: | Emerging Microbes and Infections, Vol 7, Iss 1, Pp 1-12 (2018) Emerging Microbes & Infections |
| ISSN: | 2222-1751 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|