Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Apr 4:3:60.
doi: 10.3389/fimmu.2012.00060. eCollection 2012.

Autophagy and mechanisms of effective immunity

Justine D Mintern  1 , Jose A Villadangos
Affiliations

Autophagy and mechanisms of effective immunity

Justine D Mintern et al. Front Immunol. .

Abstract

Macroautophagy (autophagy) is a cellular pathway facilitating several critical functions. First, autophagy is a major pathway of degradation. It enables elimination of microbes that have invaded intracellular compartments. In addition, it promotes degradation of damaged cellular content, thereby acting to limit inflammatory signals. Second, autophagy is a major trafficking pathway, shuttling content between the cytosol and the lysosomal compartment. Given these two key roles, autophagy can have significant and sometimes unexpected consequences on mechanisms that initiate robust immunity. Here, we will discuss the impact of autophagy on pathways of innate and adaptive immune responses including microbe elimination, inflammatory cytokine production, antigen processing and T and B lymphocyte immunity.

Keywords: T lymphocytes; adaptive immunity; antigen presentation; autophagy; innate immunity.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Role of autophagy during innate immunity. “Xenophagy” eliminates intracellular microbes. Autophagy limits inflammatory cytokine production by ensuring removal of dysfunctional organelles, including mitochondria. Accumulation of damaged mitochondria results in increased reactive oxygen species (ROS) and the escape of mitochondrial DNA into the cytosol. These are triggers of the inflammasome and interleukin-1β (IL-1β) production. Inflammasomes are targeted for degradation by autophagy. Proteins in the autophagy machinery bind to and inhibit signaling of key proteins in the type I interferon pathway, retinoic acid inducible gene-I (RIG-I) and the signaling molecule IFNβ promoter stimulator-1 (IPS-1).
Figure 2
Figure 2
Autophagy modulation of adaptive immunity. Autophagy is a significant trafficking pathway for the delivery of cytosolic antigen to the MHCII loading compartment in antigen presenting cells. In addition, proteins in the autophagy machinery contribute to phagocytosis of extracellular antigen. In lymphocytes, the role of autophagy in eliminating damaged organelles promotes cell survival.
See this image and copyright information in PMC

References

    1. Bernales S., McDonald K. L., Walter P. (2006). Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol. 4, e423.10.1371/journal.pbio.0040423 - DOI - PMC - PubMed
    1. Birmingham C. L., Smith A. C., Bakowski M. A., Yoshimori T., Brumell J. H. (2006). Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J. Biol. Chem. 281, 11374–1138310.1074/jbc.M509157200 - DOI - PubMed
    1. Blanchet F. P., Moris A., Nikolic D. S., Lehmann M., Cardinaud S., Stalder R., Garcia E., Dinkins C., Leuba F., Wu L., Schwartz O., Deretic V., Piguet V. (2010). Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. Immunity 32, 654–66910.1016/j.immuni.2010.04.011 - DOI - PMC - PubMed
    1. Brazil M. I., Weiss S., Stockinger B. (1997). Excessive degradation of intracellular protein in macrophages prevents presentation in the context of major histocompatibility complex class II molecules. Eur. J. Immunol. 27, 1506–151410.1002/eji.1830270629 - DOI - PubMed
    1. Cadwell K., Liu J. Y., Brown S. L., Miyoshi H., Loh J., Lennerz J. K., Kishi C., Kc W., Carrero J. A., Hunt S., Stone C. D., Brunt E. M., Xavier R. J., Sleckman B. P., Li E., Mizushima N., Stappenbeck T. S., Virgin H. W. IV. (2008). A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456, 259–26310.1038/nature07416 - DOI - PMC - PubMed