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Journal of Neuroimmune Pharmacology

, Volume 6, Issue 3, pp 362–370 | Cite as

M. tuberculosis H37Rv Infection of Chinese Rhesus Macaques

  • Jing Zhang
  • Yan-Qing Ye
  • Yong Wang
  • Ping-Zheng Mo
  • Qiao-Yang Xian
  • Yan Rao
  • Rong Bao
  • Ming Dai
  • Jun-Yan Liu
  • Ming Guo
  • Xin Wang
  • Zhi-Xiang Huang
  • Li-Hua Sun
  • Zhi-Jiao TangEmail author
  • Wen-Zhe HoEmail author
ORIGINAL ARTICLE

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.

Keywords

Mycobacterium tuberculosis Non-human primates Chinese rhesus macaques 

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

Notes

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.

References

  1. Capuano SV 3rd, Croix DA, Pawar S, Zinovik A, Myers A, Lin PL, Bissel S, Fuhrman C, Klein E, Flynn JL (2003) Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection. Infect Immun 71:5831–5844PubMedCrossRefGoogle Scholar
  2. Chaparas SD, Good RC, Janicki BW (1975) Tuberculin-induced lymphocyte transformation and skin reactivity in monkeys vaccinated or not vaccinated with Bacille Calmette-Guerin, then challenged with virulent Mycobacterium tuberculosis. Am Rev Respir Dis 112:43–47PubMedGoogle Scholar
  3. Dietrich G, Viret JF, Hess J (2003) Mycobacterium bovis BCG-based vaccines against tuberculosis: novel developments. Vaccine 21:667–670PubMedCrossRefGoogle Scholar
  4. Good RC (1968) Biology of the mycobacterioses. Simian tuberculosis: immunologic aspects. Ann NY Acad Sci 154:200–213PubMedCrossRefGoogle Scholar
  5. Gormus BJ, Blanchard JL, Alvarez XH, Didier PJ (2004) Evidence for a rhesus monkey model of asymptomatic tuberculosis. J Med Primatol 33:134–145PubMedCrossRefGoogle Scholar
  6. Gupta UD, Katoch VM (2005) Animal models of tuberculosis. Tuberculosis (Edinb) 85:277–293CrossRefGoogle Scholar
  7. Helke KL, Mankowski JL, Manabe YC (2006) Animal models of cavitation in pulmonary tuberculosis. Tuberculosis (Edinb) 86:337–348CrossRefGoogle Scholar
  8. Langermans JA, Andersen P, van Soolingen D, Vervenne RA, Frost PA, van der Laan T, van Pinxteren LA, van den Hombergh J, Kroon S, Peekel I, Florquin S, Thomas AW (2001) Divergent effect of Bacillus Calmette-Guerin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species: implications for primate models in tuberculosis vaccine research. Proc Natl Acad Sci USA 98:11497–11502PubMedCrossRefGoogle Scholar
  9. Lin PL, Pawar S, Myers A, Pegu A, Fuhrman C, Reinhart TA, Capuano SV, Klein E, Flynn JL (2006) Early events in Mycobacterium tuberculosis infection in cynomolgus macaques. Infect Immun 74:3790–3803PubMedCrossRefGoogle Scholar
  10. Ribi E, Anacker RL, Barclay WR, Brehmer W, Harris SC, Leif WR, Simmons J (1971) Efficacy of mycobacterial cell walls as a vaccine against airborne tuberculosis in the rhesus monkey. J Infect Dis 123:527–538PubMedCrossRefGoogle Scholar
  11. Sugawara I, Li Z, Sun L, Udagawa T, Taniyama T (2007) Recombinant BCG Tokyo (Ag85A) protects cynomolgus monkeys (Macaca fascicularis) infected with H37Rv Mycobacterium tuberculosis. Tuberculosis (Edinb) 87:518–525CrossRefGoogle Scholar
  12. Sugawara I, Sun L, Mizuno S, Taniyama T (2009) Protective efficacy of recombinant BCG Tokyo (Ag85A) in rhesus monkeys (Macaca mulatta) infected intratracheally with H37Rv Mycobacterium tuberculosis. Tuberculosis (Edinb) 89:62–67CrossRefGoogle Scholar
  13. Trichel AM, Rajakumar PA, Murphey-Corb M (2002) Species-specific variation in SIV disease progression between Chinese and Indian subspecies of rhesus macaque. J Med Primatol 31:171–178PubMedCrossRefGoogle Scholar
  14. UNAIDS (2010). The Joint United Nations Programme on HIV/AIDS. HIV and tuberculosis: ensuring universal access and protection of human rights. http://data.unaids.org/pub/ExternalDocument/2010/20100324_unaidsrghrtsissuepapertbhrts_en.pdf
  15. Walsh GP, Tan EV, Dela Cruz EC, Abalos RM, Villahermosa LG, Young LJ, Cellona RV, Nazareno JB, Horwitz MA (1996) The Philippine cynomolgus monkey (Macaca fasicularis) provides a new nonhuman primate model of tuberculosis that resembles human disease. Nat Med 2:430–436PubMedCrossRefGoogle Scholar
  16. WHO (2009). Report: global tuberculosis control—epidemiology, strategy, financing. http://www.who.int/tb/publications/global_report/2009/index.html

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jing Zhang
    • 1
  • Yan-Qing Ye
    • 2
  • Yong Wang
    • 1
  • Ping-Zheng Mo
    • 2
  • Qiao-Yang Xian
    • 1
  • Yan Rao
    • 1
  • Rong Bao
    • 1
  • Ming Dai
    • 1
  • Jun-Yan Liu
    • 1
  • Ming Guo
    • 1
  • Xin Wang
    • 1
  • Zhi-Xiang Huang
    • 1
  • Li-Hua Sun
    • 1
  • Zhi-Jiao Tang
    • 1
    Email author
  • Wen-Zhe Ho
    • 1
    • 3
    Email author
  1. 1.ABSL-3 LaboratoryWuhan UniversityHubeiPeople’s Republic of China
  2. 2.Department of RespirationZhongnan Hospital, Wuhan UniversityHubeiPeople’s Republic of China
  3. 3.Department of Pathology and Laboratory MedicineTemple University School of MedicinePhiladelphiaUSA

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