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Most of the new tuberculosis(TB)vaccine candidates are tested in nonhuman primates(NHP)using the laboratory M.tb strains(H37Rv or Erdman).However,the clinical isolates and laboratory stains have been shown to display differing genotypes and phenotypes.Thus,it is necessary to examine clinical isolates of M.tb in a(NHP)model that can demonstrate latent TB infection(LTBI),a major reservoir for a constant source of M.tb transmission.It has been suggested that cynomolgus macaques are less susceptible to M.tb infection than rhesus macaques.We thus examined M.tb infection of Chinese cynomolgus macaques.Methods: Six Chinese cynomolgus macaques were infected with a low dose(34CFU)of M.tb Erdman strain via bronchoscopy.In addition,another six Chinese cynomolgus macaques were infected with 500CFU of a clinical multidrug-resistant(MDR)M.tb isolate,which showed the resistance to Isoniazid,Rifampin,Streptomycin and Ofloxacin.Animals were monitored daily for clinical symptoms(appetite loss,weight,breathing difficulty and coughing).The clinical analyses(Chest X-rays,CT scan,ESR,CRP,TST,ELISPOT)were performed monthly.Bronchoalveolar lavage fluid(BALF)was collected monthly and cultured for M.tb.In addition,flow cytometry was performed to examine the expression of intracellular cytokines(IFN-γ,TNF-α and IL-22).Results: Five animals infected with the MDR Mtb had appetite loss,three of which had elevated ESR and CRP.X-rays and CT imaging revealed lesions in the lungs of these animals.The animal with the highest CRP level started coughing at week 12 and succumbed to TB at week 18postinfection.Necropsy of this animal revealed granulomas(1-3mm)in all seven lung lobes,spleen and liver.In addition,caseation of granulomas was found in the right lower and accessory lobes.All six animals had M.tb positive BALF as early as 4 weeks postinfection.M.tb cultures were positive in the lung tissues from all six animals.Out of six animals infected with Mtb Erdman strain,three developed active infection and died 7-8 months postinfection.Other three animals appeared to have latent M.tb infection as they had positive TST and M.tb specific IFN-γ,but little clinical signs of TB disease during the course of this study.Discussion and Conclusion: Cynomolgus macaques were successfully infected with a MDR Mtb strain.The infected animals represented the spectrum of human TB disease,as they developed variable disease progression seen in humans(latent,chronic and acute TB).In addition,our data indicate a low-dose M.tb Erdman strain infection of cynomolgus macaques of Chinese origin is suitable for establishing latent M.tb infection.