» Articles » PMID: 21167273

Mycobacterium Avium Uses Apoptotic Macrophages As Tools for Spreading

Overview
Journal Microb Pathog
Date 2010 Dec 21
PMID 21167273
Citations 42
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Mycobacterium avium (MAC) lives and replicates in macrophages and causes disseminated disease in immunocompromised individuals. As a host response to control disease, many macrophages become apoptotic a few days after MAC infection. In this study, we hypothesized that MAC can survive autophagic and apoptotic macrophages and spread.

Methods: Electron, time-lapse video, fluorescence microscopy. Apoptosis was determined by ELISA and TUNEL assays. Autophagy was seen by migration of LC3-1.

Results: Apoptotic macrophages harbor chiefly viable MAC. MAC escapes both the vacuole and the macrophage once apoptosis is triggered, leaving the bacteria free to infect nearby macrophages in the process of spreading. In addition, some MAC species will have apoptotic bodies and are released in healthy macrophages following apoptotic body ingestion. Because autophagy precedes apoptosis, it was established that heat-killed MAC, and viable MAC induces autophagy in macrophages at similar rates, but MAC still survives.

Conclusion: MAC spreading from cell-to-cell is triggered by the macrophage's attempt to kill the bacterium, undergoing apoptosis.

Citing Articles

Exploring the Chemical Space of Mycobacterial Oxidative Phosphorylation Inhibitors Using Molecular Modeling.

Matar I, Dong Z, Matta C ChemMedChem. 2024; 19(22):e202400303.

PMID: 39302818 PMC: 11581423. DOI: 10.1002/cmdc.202400303.


Itaconic acid inhibits nontuberculous mycobacterial growth in pH dependent manner while 4-octyl-itaconic acid enhances THP-1 clearance of nontuberculous mycobacteria in vitro.

Breen P, Zimbric M, Caverly L PLoS One. 2024; 19(5):e0303516.

PMID: 38728330 PMC: 11086914. DOI: 10.1371/journal.pone.0303516.


Additive Effects of Cyclic Peptide [R4W4] When Added Alongside Azithromycin and Rifampicin against Infection.

Kelley M, Sasaninia K, Abnousian A, Badaoui A, Owens J, Beever A Pathogens. 2023; 12(8).

PMID: 37624017 PMC: 10459066. DOI: 10.3390/pathogens12081057.


subsp. Candidate Vaccine Strains Are Pro-apoptotic in RAW 264.7 Murine Macrophages.

Barletta R, Bannantine J, Stabel J, Muthukrishnan E, Anderson D, Dutta E Vaccines (Basel). 2023; 11(6).

PMID: 37376474 PMC: 10305633. DOI: 10.3390/vaccines11061085.


Modulating macrophage function to reinforce host innate resistance against complex infection.

Park H, Lee W, Choi S, Jung M, Shin M, Shin S Front Immunol. 2022; 13:931876.

PMID: 36505429 PMC: 9730288. DOI: 10.3389/fimmu.2022.931876.


References
1.
Flesselles B, Anand N, Remani J, Loosmore S, Klein M . Disruption of the mycobacterial cell entry gene of Mycobacterium bovis BCG results in a mutant that exhibits a reduced invasiveness for epithelial cells. FEMS Microbiol Lett. 1999; 177(2):237-42. DOI: 10.1111/j.1574-6968.1999.tb13738.x. View

2.
Steinert M, Birkness K, White E, Fields B, Quinn F . Mycobacterium avium bacilli grow saprozoically in coculture with Acanthamoeba polyphaga and survive within cyst walls. Appl Environ Microbiol. 1998; 64(6):2256-61. PMC: 106308. DOI: 10.1128/AEM.64.6.2256-2261.1998. View

3.
Bermudez L, Petrofsky M, Sangari F . Intracellular phenotype of Mycobacterium avium enters macrophages primarily by a macropinocytosis-like mechanism and survives in a compartment that differs from that with extracellular phenotype. Cell Biol Int. 2004; 28(5):411-9. DOI: 10.1016/j.cellbi.2004.03.010. View

4.
Stamm L, Morisaki J, Gao L, Jeng R, McDonald K, Roth R . Mycobacterium marinum escapes from phagosomes and is propelled by actin-based motility. J Exp Med. 2003; 198(9):1361-8. PMC: 2194249. DOI: 10.1084/jem.20031072. View

5.
Monack D, Mecsas J, Bouley D, Falkow S . Yersinia-induced apoptosis in vivo aids in the establishment of a systemic infection of mice. J Exp Med. 1998; 188(11):2127-37. PMC: 2212385. DOI: 10.1084/jem.188.11.2127. View