Autophagy--A free meal in sickness-associated anorexia

Abstract

Activation of the immune system is metabolically costly, yet a hallmark of an infection is a reduction in appetite with a subsequent reduction in metabolite provision. What is the functional value of decreasing nutrient intake when an infection imposes large demands on metabolic parameters? Here, we propose that sickness-associated anorexia (SAA) upregulates the ancient process of autophagy systemically, thereby profoundly controlling not only immune- but also nonimmune-competent cells. This allows an advanced impact on the resolution of an infection through direct pathogen killing, enhancement of epitope presentation and the contribution toward the clearance of noxious factors. By rendering a 'free meal,' autophagy is thus most fundamentally harnessed during an anorexic response in order to promote both host tolerance and resistance. These findings strongly suggest a reassessment of numerous SAA-related clinical applications and a re-evaluation of current efforts in patient care.

Keywords: anorexia; autophagy; infection; sickness behavior; xenophagy.

Figure 1.

The autophagic machinery deployed in housekeeping functions is fundamentally implicated in pathogen clearance and subsequent loading and expression of pathogen epitopes onto MHC II complexes. Pathogens have evolved numerous mechanisms to avoid autophagic degradation. Note, in addition to being phagocytosed, viruses and bacteria have evolved numerous strategies to gain entry into nonphagocytic cells via endocytosis. Endosomes can be targeted by autophagy or fuse with autophagosomes to form amphisomes. Regardless, similar autophagic components are implicated in these processes.

Figure 2.

During an infection, immune effectors remodel the nutrient context in order to induce and maintain heightened autophagic flux.