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M. tuberculosis H37Rv Infection of Chinese Rhesus Macaques

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Abstract

Mycobacterium tuberculosis is the most common communicable infectious disease worldwide and the top killer of human immunodeficiency virus (HIV)-infected people. Because of common dual HIV and M. tuberculosis infections, the emergence of multidrug-resistant M. tuberculosis strains, the lack of effective vaccination, the morbidity, and the mortality of M. tuberculosis infection are increasing sharply. Therefore, there is an urgent need for vaccine and drug development against M. tuberculosis infection. These require appropriate animal models that closely resemble human disease. To this end, we infected Chinese rhesus macaques with the M. tuberculosis H37Rv strain. Bronchoscopy was used to inoculate nine monkeys with different doses of M. tuberculosis H37Rv strain. Regardless of the M. tuberculosis dose, all monkeys were infected successfully. This was shown by clinical, laboratory, and histopathology assessments. Among nine infected monkeys, six developed acute rapid progressive tuberculosis and the remaining animals mirrored early-stage chronic disease. These data, taken together, demonstrate that Chinese rhesus macaques are highly susceptible to M. tuberculosis infection and develop similar manifestations of disease that are seen in humans. This model affords new opportunities for studies of M. tuberculosis disease pathology and therapeutics.

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Abbreviations

ABSL:

Animal biosafety level

CRP:

C-reactive protein

CFU:

Colony forming units

ESR:

Erythrocyte sedimentation rate

OT:

Old tuberculin

PI:

Post-inoculation

SIV:

Simian immunodeficiency virus

TST:

Tuberculin skin test

TB:

Tuberculosis

WHO:

World Health Organization

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Acknowledgments

The authors thank Dr. Sugawara I (the Research Institute of Tuberculosis, Tokyo) for providing the M. tuberculosis H37Rv strain. We are grateful to Junhui Wu for his kind review of the manuscript. This study was supported by the grants (2009ZX10004-402) from the Mega-Projects of Science Research for the 11th Five-Year Plan, China, 2009ZX10004-402.

Conflicts of interest

There are no any ethical or financial conflicts of interest for all authors. The corresponding authors, Drs. Wenzhe Ho and Zhi-Jiao Tang, take responsibility on behalf of all authors for the authorship, authenticity, and integrity of this manuscript.

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Correspondence to Zhi-Jiao Tang or Wen-Zhe Ho.

Additional information

Jing Zhang and Yan-Qing Ye contributed equally to this study.

Part of this work was presented in the 15th SNIP Scientific Conference, Wuhan City, Hubei, P.R. China, April 21–24, 2009.

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Zhang, J., Ye, YQ., Wang, Y. et al. M. tuberculosis H37Rv Infection of Chinese Rhesus Macaques. J Neuroimmune Pharmacol 6, 362–370 (2011). https://doi.org/10.1007/s11481-010-9245-4

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