M. tuberculosis H37Rv Infection of Chinese Rhesus Macaques

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.

Monkey Models of Tuberculosis: Lessons Learned

“…A series of subsequent investigations were dedicated to macaque research to assess novel TB vaccines and drugs, as well as to gain an understanding of the pathogenesis of M. tuberculosis infection and reactivation. Figures 2 and 3 abridge the RM (13,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) and CM (10,15,25,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59) models of experimental M. tuberculosis infection after the Golden Age, from 2001 to 2014.…”

“…The majority of NHP models of M. tuberculosis infection have involved either CM or Indian RM, except for at least five reported research projects which used Chinese RM in Wuhan, China (34,35), Solna, Sweden (28,29), and Rijswijk, the Netherlands (30). So far within the scientific literature illustrating macaque models of M. tuberculosis infection, the routes of inoculation have included i.b.…”

“…used as a viable model of acute TB (34). Chinese RM are highly susceptible to M. tuberculosis infection and develop active TB regardless of the dose of strain H37Rv used (34).…”

“…Chinese RM are highly susceptible to M. tuberculosis infection and develop active TB regardless of the dose of strain H37Rv used (34). In an attempt to improve the methods to monitor the progression of TB disease, Helke et al (27) from the Oregon NPRC showed that use of highresolution radiographic and fine immunologic studies helped define the disease status in RM as in humans.…”

Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques

“…1A and B) implied that this dose might be too high for future studies that fully replicate the kinetics of an anti-M. tuberculosis T-cell response. In Chinese cynomolgus macaques, animals develop a spectrum of infection outcomes when a lower dose (ϳ25 CFU) of M. tuberculosis Erdman is administered (3,23), and the severity of TB disease tends to correlate with the infectious dose in rhesus macaques (24,25). With the goal of using MCMs to study T-cell responses over the entire course of TB and for all disease outcomes, we sought to confirm that a lower dose of M. tuberculosis also elicited epitope-specific T cells.…”