Development of a neonatal non human primate model to study latent Mycobacterium tuberculosis infection
Mycobacterium tuberculosis is the predominant cause of human tuberculosis (TB). In 2010 there were an estimated 8.8 million new cases of TB and 1.4 million deaths. It is estimated that one third of the population is latently infected with TB, of which∼10% will develop active disease during their lifetime. Tuberculosis is the leading cause of death in AIDS patients worldwide. Co-infection with M. tuberculosis and HIV is an increasing global emergency. There is an urgent need for a clinically relevant newborn macaque model to study TB infection in newborn/infants. We successfully developed a neonatal macaque model that mimics the latent disease as seen in human infants. This model presents a new strategy to characterize M. tuberculosis infection in newborns/infants and further establish a TB co-infection model for pediatric AIDS. Aerosol versus broncho-alveolar routes were applied to study M. tuberculosis infections. M. tuberculosis Erdman and H37Rv strains were used in order to produce an active/progressive or latent/asymptomatic course of disease. Using ELISPOT assays, we found that IL-12 production correlated with early M. tuberculosis infection as seen with routine chest X-rays. Specific cellular immune response was seen after 4-6 weeks post primary M. tuberculosis infection . Our data confirmed that newborn macaques are highly susceptible to M. tuberculosis and can serve as a suitable animal model to study TB pathogenesis.