Two recent papers have provided further details on the role of autophagy as an innate immune defence mechanism against bacterial pathogens.

Autophagy — literally 'self-eating' — is the process by which eukaryotic cells remove defective or excess organelles and recycle the constituent macromolecules in times of stress. A double-membrane-bound structure known as the autophagosome forms de novo and, after formation, fuses with endosomal vesicles, creating intermediate autophagosomes that go on to fuse with lysosomes, forming mature autolysosomes that can degrade their contents. Autophagy has previously been recognized as an effective method of defence against some intracellular pathogens including Listeria monocytogenes. Now, new research proves that autophagy can also help clear group A Streptococcus (GAS) and Mycobacterium tuberculosis infections.

In the first study, published in Science, Nakagawa et al., using the autophagosome-specific marker LC3 tagged with GFP, found that, in HeLa cells, intracellular GAS localized in autophagosome-like compartments. Quantitative analysis of this localization within a second cell line, embryonic stem (ES) cells — notably, like HeLa cells, these are non-phagocytic — showed that ∼80% of GAS were found within these compartments. The fact that the levels of the autophagosome-specific form of LC3 increased after infection suggested that the autophagy being observed was induced, and this was confirmed by analysing cells deficient in autophagosome formation. Additionally, the results obtained suggested that GAS were killed within these autophagosome-like structures.

In the second study, published online in Cell, Gutierrez et al. have shown that autophagy can inhibit the survival of M. tuberculosis within infected macrophages. The induction of autophagy by physiological or pharmacological signals was shown to induce increased acidification and subsequent maturation of mycobacterial-containing phagosomes, resulting in intracellular killing of the mycobacteria. Additionally, these researchers found that autophagy was also stimulated by IFN-γ, thus shedding light on the anti-mycobacterial action of this cytokine, which until now has not been fully understood. The small cytoplasmic GTPase LRG-47 was also identified as being involved in the IFN-γ-dependent induction of autophagy.

Some bacterial pathogens have evolved strategies to avoid or subvert autophagic destruction. These latest results suggest that for GAS and M. tuberculosis, in certain circumstances autophagy can be a useful addition to the host innate immune armamentarium.