Factor H Family Proteins in Complement Evasion of Microorganisms.

Mihály Józsi

doi:10.3389/fimmu.2017.00571

Abstract

Human-pathogenic microbes possess various means to avoid destruction by our immune system. These include interactions with the host complement system that may facilitate pathogen entry into cells and tissues, expression of molecules that defuse the effector complement components and complexes, and acquisition of host complement inhibitors to downregulate complement activity on the surface of the pathogen. A growing number of pathogenic microorganisms have acquired the ability to bind the complement inhibitor factor H (FH) from body fluids and thus hijack its host protecting function. In addition to FH, binding of FH-related (FHR) proteins was also demonstrated for several microbes. Initial studies assumed that these proteins are complement inhibitors similar to FH. However, recent evidence suggests that FHR proteins may rather enhance complement activation both directly and also by competing with the inhibitor FH for binding to certain ligands and surfaces. This mini review focuses on the role of the main alternative pathway regulator FH in host–pathogen interactions, as well as on the emerging role of the FHR proteins as enhancers of complement activation.

Highlights

Mihály Józsi*Human-pathogenic microbes possess various means to avoid destruction by our immune system
Innate and adaptive immune mechanisms work in a collaborative manner to effectively eliminate invading microorganisms and develop immune memory
Because complement control protein (CCP) 6–7 and 19–20 of factor H (FH) mediate interactions of the complement regulator with C3b, the pentraxins C-reactive protein (CRP) and pentraxin 3 (PTX3), MDA epitopes, host cells, and basement membranes, due to the potentially overlapping ligand-binding capacity associated with the homologous domains, FHRs could interfere with FH functions through competition [23]

Summary

Mihály Józsi*

Human-pathogenic microbes possess various means to avoid destruction by our immune system These include interactions with the host complement system that may facilitate pathogen entry into cells and tissues, expression of molecules that defuse the effector complement components and complexes, and acquisition of host complement inhibitors to downregulate complement activity on the surface of the pathogen. Recent evidence suggests that FHR proteins may rather enhance complement activation both directly and by competing with the inhibitor FH for binding to certain ligands and surfaces. This mini review focuses on the role of the main alternative pathway regulator FH in host–pathogen interactions, as well as on the emerging role of the FHR proteins as enhancers of complement activation

INTRODUCTION

THE HUMAN FH PROTEIN FAMILY

FHRs BINDING TO MICROBES

CONCLUSION AND OUTLOOK