Dataset Information

Autophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus Macaques.

ABSTRACT: Non-human primates, notably rhesus macaques (Macaca mulatta, RM), provide a robust experimental model to investigate the immune response to and effective control of Mycobacterium tuberculosis infections. Changes in the function of immune cells and immunosenescence may contribute to the increased susceptibility of the elderly to tuberculosis. The goal of this study was to examine the impact of age on M. tuberculosis host-pathogen interactions following infection of primary alveolar macrophages derived from young and aged rhesus macaques. Of specific interest to us was whether the mycobactericidal capacity of autophagic macrophages was reduced in older animals since decreased autophagosome formation and autophagolysosomal fusion has been observed in other cells types of aged animals. Our data demonstrate that alveolar macrophages from old RM are as competent as those from young animals for autophagic clearance of M. tuberculosis infection and controlling mycobacterial replication. While our data do not reveal significant differences between alveolar macrophage responses to M. tuberculosis by young and old animals, these studies are the first to functionally characterize autophagic clearance of M. tuberculosis by alveolar macrophages from RM.

SUBMITTER: Pacheco SA

PROVIDER: S-EPMC3688994 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Autophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus Macaques.

Pacheco Sophia A SA Powers Katelyn M KM Engelmann Flora F Messaoudi Ilhem I Purdy Georgiana E GE

PloS one 20130618 6

Non-human primates, notably rhesus macaques (Macaca mulatta, RM), provide a robust experimental model to investigate the immune response to and effective control of Mycobacterium tuberculosis infections. Changes in the function of immune cells and immunosenescence may contribute to the increased susceptibility of the elderly to tuberculosis. The goal of this study was to examine the impact of age on M. tuberculosis host-pathogen interactions following infection of primary alveolar macrophages de ...[more]

PMID: 23825603

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Project description:The factors that determine host susceptibility to tuberculosis (TB) are poorly defined. The microbiota has been identified as a key influence on the nutritional, metabolic, and immunological status of the host, although its role in the pathogenesis of TB is currently unclear. Here, we investigated the influence of Mycobacterium tuberculosis exposure on the microbiome and conversely the impact of the intestinal microbiome on the outcome of M. tuberculosis exposure in a rhesus macaque model of tuberculosis. Animals were infected with different strains and doses of M. tuberculosis in three independent experiments, resulting in a range of disease severities. The compositions of the microbiotas were then assessed using a combination of 16S rRNA and metagenomic sequencing in fecal samples collected pre- and postinfection. Clustering analyses of the microbiota compositions revealed that alterations in the microbiome after M. tuberculosis infection were of much lower magnitude than the variability seen between individual monkeys. However, the microbiomes of macaques that developed severe disease were noticeably distinct from those of the animals with less severe disease as well as from each other. In particular, the bacterial families Lachnospiraceae and Clostridiaceae were enriched in monkeys that were more susceptible to infection, while numbers of Streptococcaceae were decreased. These findings in infected nonhuman primates reveal that certain baseline microbiome communities may strongly associate with the development of severe tuberculosis following infection and can be more important disease correlates than alterations to the microbiota following M. tuberculosis infection itself.IMPORTANCE Why some but not all individuals infected with Mycobacterium tuberculosis develop disease is poorly understood. Previous studies have revealed an important influence of the microbiota on host resistance to infection with a number of different disease agents. Here, we investigated the possible role of the individual's microbiome in impacting the outcome of M. tuberculosis infection in rhesus monkeys experimentally exposed to this important human pathogen. Although M. tuberculosis infection itself caused only minor alterations in the composition of the gut microbiota in these animals, we observed a significant correlation between an individual monkey's microbiome and the severity of pulmonary disease. More importantly, this correlation between microbiota structure and disease outcome was evident even prior to infection. Taken together, our findings suggest that the composition of the microbiome may be a useful predictor of tuberculosis progression in infected individuals either directly because of the microbiome's direct influence on host resistance or indirectly because of its association with other host factors that have this influence. This calls for exploration of the potential of the microbiota composition as a predictive biomarker through carefully designed prospective studies.

Dataset Information

Autophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus Macaques.

Publications

Autophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus Macaques.

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