Establishment of a neonatal rhesus macaque model to study Mycobacterium tuberculosis infection.
Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4-6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS.
['Cepeda|Magdalena|M|', 'Salas|Mary|M|', 'Folwarczny|Jessica|J|', 'Leandro|Ana C|AC|', 'Hodara|Vida L|VL|', 'de la Garza|Melissa A|MA|', 'Dick|Edward J|EJ|', 'Owston|Michael|M|', 'Armitige|Lisa Y|LY|', 'Gauduin|Marie-Claire|MC|']
D056704:Adaptive Immunity D000280:Administration, Inhalation D000818:Animals D000831:Animals, Newborn D000942:Antigens, Bacterial D001831:Body Temperature D001835:Body Weight D060085:Coinfection D004195:Disease Models, Animal D058501:Enzyme-Linked Immunospot Assay D005434:Flow Cytometry D007111:Immunity, Cellular D018664:Interleukin-12 D008253:Macaca mulatta D009169:Mycobacterium tuberculosis D016097:Simian Acquired Immunodeficiency Syndrome D014397:Tuberculosis, Pulmonary
rhesus macaque TB newborn Ghon focus ELISPOT IL-12