Hypothesis

New insights into the possible role of bacteriophages in host defense and disease

Andrzej Gorski^1,2, Krystyna Dabrowska¹, Kinga Switala-Jeleń¹, Maria Nowaczyk², Beata Weber-Dabrowska¹, Janusz Boratynski¹, Joanna Wietrzyk¹ and Adam Opolski¹

¹L.Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland

²Transplantation Institute, The Medical Academy of Warsaw, 02-006 Warsaw, Poland

Medical Immunology 2003, 2:2doi:10.1186/1476-9433-2-2

Published:	14 February 2003

Abstract

Background

While the ability of bacteriophages to kill bacteria is well known and has been used in some centers to combat antibiotics – resistant infections, our knowledge about phage interactions with mammalian cells is very limited and phages have been believed to have no intrinsic tropism for those cells.

Presentation of the hypothesis

At least some phages (e.g., T4 coliphage) express Lys-Arg-Gly (KGD) sequence which binds β3 integrins (primarily αIIbβ3). Therefore, phages could bind β3+ cells (platelets, monocytes, some lymphocytes and some neoplastic cells) and downregulate activities of those cells by inhibiting integrin functions.

Testing the hypothesis

Binding of KGD+ phages to β3 integrin+ cells may be detected using standard techniques involving phage – mediated bacterial lysis and plaque formation. Furthermore, the binding may be visualized by electron microscopy and fluorescence using labelled phages. Binding specificity can be confirmed with the aid of specific blocking peptides and monoclonal antibodies. In vivo effects of phage – cell interactions may be assessed by examining the possible biological effects of β3 blockade (e.g., anti-metastatic activity).

Implication of the hypothesis

If, indeed, phages can modify functions of β3+ cells (platelets, monocytes, lymphocytes, cancer cells) they could be important biological response modifiers regulating migration and activities of those cells. Such novel understanding of their role could open novel perspectives in their potential use in treatment of cardiovascular and autoimmune disease, graft rejection and cancer.