Cross-talk between pathogen recognizing Toll-like receptors and immunoglobulin Fc receptors in immunity.
The individual role of pathogen-binding Toll-like receptors (TLRs) and antibody-binding Fc receptors (FcRs) during pathogenic infections has been studied extensively. However, combined activation of these different receptor classes has received little attention, even though they are triggered simultaneously when immune cells bind antibody-opsonized pathogens. In the last few years, it has become evident that joined activation of TLRs and FcRs substantially tailors inflammatory immune responses, which is an efficient and controlled mechanism of the host to act upon invading pathogens. In this review, we discuss the mechanisms of cross-talk between different TLRs and FcRs and the resulting inflammatory immune responses. Furthermore, we propose how chronic activation via this cross-talk might be detrimental in inflammatory (auto) immune diseases. We conclude with the potential exploitation of the interplay between TLRs and FcRs for monoclonal antibody therapy to target tumors. Future interests in this field of research include establishing a more detailed and mechanistic understanding of the mode of action of TLR and FcR cross-talk and exploration of its physiological importance in health and disease. This may furthermore open up novel therapeutic options for intervention in inflammatory diseases or cancer.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Marjolein
M
van Egmond
Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Gestur
G
Vidarsson
Tumor Biology Section, Department of Otolaryngology/Head-Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Jantine E
JE
Bakema
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D054884:Host-Pathogen Interactions; D006801:Humans; D007109:Immunity; D007136:Immunoglobulins / Q000276:immunology* / Q000378:metabolism*; D007239:Infections / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D011485:Protein Binding; D011961:Receptors, Fc / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007136:Immunoglobulins; D011961:Receptors, Fc; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors
Fc receptors; TLR; antibody; cancer; cytokine; inflammation