title: Establishment of a neonatal rhesus macaque model to study Mycobacterium tuberculosis infection.
abstract: 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.
authors.affiliation: Texas Biomedical Research Institute, Department of Virology and Immunology, San Antonio, Texas 78227, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cepeda
authors.affiliation: Texas Biomedical Research Institute, Department of Virology and Immunology, San Antonio, Texas 78227, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Salas
authors.affiliation: Texas Biomedical Research Institute, Department of Virology and Immunology, San Antonio, Texas 78227, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Folwarczny
authors.affiliation: Texas Biomedical Research Institute, Department of Genetic, San Antonio, Texas 78227, USA.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Leandro
authors.affiliation: Texas Biomedical Research Institute, Department of Virology and Immunology, San Antonio, Texas 78227, USA; Southwest National Primate Research Center, San Antonio, Texas 78227, USA.
authors.forename: Vida L
authors.initials: VL
authors.lastname: Hodara
authors.affiliation: Southwest National Primate Research Center, San Antonio, Texas 78227, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: de la Garza
authors.affiliation: Southwest National Primate Research Center, San Antonio, Texas 78227, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dick
authors.affiliation: Southwest National Primate Research Center, San Antonio, Texas 78227, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Owston
authors.affiliation: Heartland National TB Center, San Antonio, Texas 78223, USA; University of Texas Health Science Center, Division of Adult Infectious Diseases, Tyler, Texas 75708, USA.
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Armitige
authors.affiliation: Texas Biomedical Research Institute, Department of Virology and Immunology, San Antonio, Texas 78227, USA; Southwest National Primate Research Center, San Antonio, Texas 78227, USA. Electronic address: mcgauduin@txbiomed.org.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gauduin
mesh_terms: D056704:Adaptive Immunity; D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D000942:Antigens, Bacterial / Q000276:immunology*; D001831:Body Temperature; D001835:Body Weight; D060085:Coinfection / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000276:immunology*; D008253:Macaca mulatta; D009169:Mycobacterium tuberculosis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D018664:Interleukin-12
keywords: ELISPOT IL-12; Ghon focus; TB; newborn; rhesus macaque