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Tuberculosis (Edinb). 2013 Dec;93 Suppl:S51-9. doi: 10.1016/S1472-9792(13)70011-8.

Establishment of a neonatal rhesus macaque model to study Mycobacterium tuberculosis infection.

Author information

1
Texas Biomedical Research Institute, Department of Virology and Immunology, San Antonio, Texas 78227, USA.
2
Texas Biomedical Research Institute, Department of Genetic, San Antonio, Texas 78227, USA.
3
Texas Biomedical Research Institute, Department of Virology and Immunology, San Antonio, Texas 78227, USA; Southwest National Primate Research Center, San Antonio, Texas 78227, USA.
4
Southwest National Primate Research Center, San Antonio, Texas 78227, USA.
5
Heartland National TB Center, San Antonio, Texas 78223, USA; University of Texas Health Science Center, Division of Adult Infectious Diseases, Tyler, Texas 75708, USA.
6
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.

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.

KEYWORDS:

ELISPOT IL-12; Ghon focus; TB; newborn; rhesus macaque

PMID:
24388650
PMCID:
PMC4051704
DOI:
10.1016/S1472-9792(13)70011-8
[Indexed for MEDLINE]
Free PMC Article

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