Autophagy during common bacterial and viral infections of children.

Autophagy is a well-known survival mechanism of the cell. Autophagosomes remove excessive proteins and thereby maintain homeostasis within the cell. Autophagy is now recognized as a component of both innate and adaptive immune responses to bacterial and viral pathogens common to children. These pathogens include Streptococcus, tuberculosis, as well as hepatitis and herpes viruses. Varicella-zoster virus infection provides an excellent example of autophagy in humans, because abundant autophagosomes are easily detected in the skin vesicles of both varicella and zoster. Engineered herpes viruses, which elicit autophagy responses, are being used currently in clinical therapeutic trials against brain cancer. Furthermore, defective autophagy of bacteria may explain in part the pathogenesis of Crohn disease. However, at present, there is no single screening diagnostic assay by which to measure autophagy, as a means to investigate an etiologic role in children with an as yet undefined immunodeficiency. Instead, translational researchers are measuring individual components of the cellular autophagy pathway in both humans and animal models, to correlate autophagy responses with severity of infection. Autophagy certainly will remain a subject of immunology investigations in children in the coming decade.