1 Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, California, United States of America, 2 Rady Children’s Hospital, San Diego, California, United States of AmericaAuthor Summary Top
Macroautophagy (autophagy – ‘self-eating’, lysosome-dependent degradation and recycling of the intracellular components in response to stress) is an important host defense mechanism against viral and mycobacterial infections. Recent studies have described that activation of autophagy in macrophages reduces the viability of Mycobacterium tuberculosis and HIV due to an intimate autophagy-phagocytosis interaction. Low serum levels of the 25-hydroxycholecalciferol form of vitamin D have been associated with an increased risk for active tuberculosis and HIV disease progression as well as M. tuberculosis susceptibility. In this study, we report that the active form of vitamin D, 1α,25-dihydroxycholecalciferol inhibits the replication of HIV and M. tuberculosis in a concentration dependent manner. Moreover, by inhibiting key stages in the autophagy pathway, we demonstrate that the inhibition of HIV and mycobacterial growth during single infection or dual infection is dependent not only upon the induction of autophagy, but also through phagosomal maturation. Furthermore, through the use of RNA interference for the human cathelicidin microbial peptide we demonstrate that cathelicidin is essential for the 1α,25-dihydroxycholecalciferol induced autophagic flux and inhibition of HIV replication and mycobacterial growth. These findings suggest that the induction of autophagy has the potential to be useful in the treatment of persons co-infected with HIV and M. tuberculosis.
In the old days, tuberculosis patients were sent to sanatoriums, typically at high altitude, for lack of any better treatment. (See Mann’s The Magic Mountain.) As far as I know, it was thought that the mountain air did them good, but it seems more likely that greater solar exposure at high altitude and subsequent vitamin D production could have been at work. I don’t know whether anyone has looked into this.