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Open Access Research article

Intracellular growth of Mycobacterium avium subspecies and global transcriptional responses in human macrophages after infection

Angelika Agdestein1, Anya Jones2, Arnar Flatberg3, Tone B Johansen1, Inger Austrheim Heffernan1, Berit Djønne1, Anthony Bosco2 and Ingrid Olsen1*

Author Affiliations

1 Norwegian Veterinary Institute, PO. Box 750 Sentrum, N-0106 Oslo, Norway

2 Telethon Institute for Child Health Research, UWA Centre for Child Health Research, University of Western Australia, 100 Roberts Rd, Subiaco, WA 6008 Australia

3 Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway

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BMC Genomics 2014, 15:58  doi:10.1186/1471-2164-15-58

Published: 23 January 2014

Abstract

Background

Mycobacterium avium subsp. avium (Maa) and M. avium subsp. hominissuis (Mah) are environmental mycobacteria and significant opportunistic pathogens. Mycobacterium avium infections in humans and pigs are mainly due to Mah. It is not known whether this is caused by a difference in virulence or difference in exposure to the two subspecies. The aim of the present study was to investigate the ability of the M. avium subspecies to replicate intracellularly and to characterise the gene expression program triggered by infection of human primary macrophages.

Results

All isolates were able to invade and persist within human macrophages. However, intracellular replication was only evident in cells infected with the two Maa isolates. Transcriptional responses to the isolates were characterized by upregulation of genes involved in apoptosis, immune- and inflammatory response, signal transduction and NF-kB signaling, cell proliferation and T-cell activation. Although similar pathways and networks were perturbed by the different isolates, the response to the Maa subspecies was exaggerated, and there was evidence of increased activation of type I and II interferon signaling pathways.

Conclusion

Mycobacterium avium isolates of different genetic characteristics invaded monocytes and induced different degree of macrophage activation. Isolates of Maa were able to replicate intracellularly suggesting that differences in exposure, uptake or induction of adaptive immunity are more likely explanations for the difference in prevalence between M. avium subspecies.

Keywords:
Mycobacterium avium; Human macrophages; Gene expression