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Published on: July 9, 2014
Autophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus
Sophia A Pacheco1, Katelyn M Powers, Flora Engelmann
1Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, United States of America.
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.
Insights
Age does not impair the ability of rhesus macaque alveolar macrophages to clear Mycobacterium tuberculosis infections. This study highlights the effectiveness of these immune cells in both young and aged non-human primates.
Area of Science:
- Immunology
- Microbiology
- Aging Research
Background:
- Tuberculosis (TB) susceptibility increases with age, potentially due to immune cell dysfunction and immunosenescence.
- Non-human primates, specifically rhesus macaques (Macaca mulatta, RM), serve as a valuable model for studying TB.
- Autophagy is crucial for controlling Mycobacterium tuberculosis (M. tuberculosis) infection, but its function in aged cells is less understood.
Purpose of the Study:
- To investigate the impact of aging on host-pathogen interactions in M. tuberculosis infection.
- To determine if the autophagic capacity of alveolar macrophages from aged rhesus macaques is reduced in controlling M. tuberculosis.
Main Methods:
- Primary alveolar macrophages were isolated from young and aged rhesus macaques.
- Macrophages were infected with M. tuberculosis.
- Autophagic clearance and mycobacterial replication were assessed.
Main Results:
- Alveolar macrophages from both young and aged rhesus macaques demonstrated comparable competence in autophagic clearance of M. tuberculosis.
- No significant differences were observed in the control of mycobacterial replication between macrophages from young and old animals.
- These findings represent the first functional characterization of M. tuberculosis autophagic clearance by rhesus macaque alveolar macrophages across different age groups.
Conclusions:
- Aging does not appear to compromise the autophagic function of rhesus macaque alveolar macrophages in controlling M. tuberculosis infection.
- Rhesus macaques serve as a relevant model for studying age-related immune responses to tuberculosis.
