Surfactant protein D/anti-Fc receptor bifunctional proteins as a tool to enhance host defence

Abstract

Background: Drug-resistant pathogens are an increasing threat, particularly for hospitalised patients. In search of a new approach in pathogen targeting, we developed bifunctional proteins that combine broad spectrum pathogen recognition with efficient targeting to phagocytes. Pathogen recognition is provided by a recombinant fragment of surfactant protein D (rfSP-D) while targeting to phagocytic cells is accomplished by coupling rfSP-D to F(ab′) fragments directed against Fcα receptor I (FcαRI) or Fcγ receptor I (FcγRI). FcαRI and FcγRI are expressed on myeloid cells, and induce rapid internalisation of particles after crosslinking. Objective/methods: In this review we discuss the roles of SP-D and Fc receptors in host defence as a rationale for rfSP-D/anti-FcR bifunctional proteins. Furthermore we summarise the available data on rfSP-D/anti-FcR proteins as well as opportunities and considerations for future use of such bifunctional proteins. Results/conclusion: rfSP-D/anti-FcR bifunctional proteins could be of great value for the treatment of a variety of infectious diseases. The focus in the near future should be on proof-of-principle by testing the bifunctional proteins in different mouse models of infectious disease.

Keywords::

• broad-spectrum antimicrobial therapy
• Fc receptors
• host defence
• pathogen targeting
• surfactant protein D

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