An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery

Parker, Michael T.

An example of how a phage could affect human health is as an endogenous ligand for immune activation. It is known that humans harbor antibodies to phage proteins [67] [68] [69] [70] and that phagocytic cells of the immune system can ingest phages [71] , but whether this has any negative impact on health is unknown. Toll-like Receptors (TLRs) -7 and -9 play key roles in the production of autoantibodies, presumably via sensing of nucleic acid containing immune complexes (reviewed in [72] ). These autoantibodies could be derived from any number of endogenous sources, including those of phages. Interestingly, identifying the particular nucleic acids responsible for this activation in vivo has been challenging, though functional work has vetted this mechanism with immune complexes containing nucleic acids [73, 74] . It is possible that B-cell Receptor (BCR)-mediated endocytic or plasmacytoid dendritic cell (pDC) phagocytic internalization of phages could deliver ligands necessary for these responses. In this light, I would argue that correlating phage localization and expression with disease state is a particularly intriguing area of research moving forward. Such research may also elucidate mechanisms by which specific bacteria (and their viral cargo) are linked to autoimmune, allergic, and pathogenic phenotypes.