Eating the enemy within: autophagy in infectious diseases

Abstract

Autophagy is emerging as a central component of antimicrobial host defense against diverse viral, bacterial, and parasitic infections. In addition to pathogen degradation, autophagy has other functions during infection such as innate and adaptive immune activation. As an important host defense pathway, microbes have also evolved mechanisms to evade, subvert, or exploit autophagy. Additionally, some fungal pathogens harness autophagy within their own cells to promote pathogenesis. This review will highlight our current understanding of autophagy in infection, focusing on the most recent advances in the field, and will discuss the potential implications of these studies in the design of anti-infective therapeutics.

Figure 1

Regulation of autophagy by immune signaling pathways. Examples of positive regulators include TLRs (3, 4, and 7/8), PKR, IFNγ, and CD40. Pathways that negatively regulate autophagy include NF-κB and TH2 cytokines. The mechanisms by which all of these pathways intersect with the autophagy machinery remain unknown

Figure 2

Effector functions of autophagy in infectious diseases

Figure 3

Potential therapeutic targets in modulating autophagy in the treatment or prevention of infectious diseases. (1) Inhibition of microbial virulence factors that evade or subvert host autophagy. (2) Stimulation of autophagy with pharmacological agents (i.e., rapamycin or novel compounds such as SMERs, small molecule enhancers of rapamycin-induced autophagy). (3) Autophagy regulation through activation of innate immunity signaling receptors. (4) Vaccine enhancement by targeting antigens to the autophagy pathway by fusion with the autophagy protein, LC3. (5) Selective inhibition of microbial autophagy in eukaryotic pathogens that utilize their own autophagy as a virulence pathway