Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes.
A wide range of microorganisms can replicate in macrophages, and cell entry of these pathogens via non-neutralising IgG antibody complexes can result in increased intracellular infection through idiosyncratic Fcγ-receptor signalling. The activation of Fcγ receptors usually leads to phagocytosis. Paradoxically, the ligation of monocyte or macrophage Fcγ receptors by IgG immune complexes, rather than aiding host defences, can suppress innate immunity, increase production of interleukin 10, and bias T-helper-1 (Th1) responses to Th2 responses, leading to increased infectious output by infected cells. This intrinsic antibody-dependent enhancement (ADE) of infection modulates the severity of diseases as disparate as dengue haemorrhagic fever and leishmaniasis. Intrinsic ADE is distinct from extrinsic ADE, whereby complexes of infectious agents with non-neutralising antibodies lead to an increased number of infected cells. Intrinsic ADE might be involved in many protozoan, bacterial, and viral infections. We review insights into intracellular mechanisms and implications of enhanced pathogenesis after ligation of macrophage Fcγ receptors by infectious immune complexes.
Halstead
Scott B
SB
International Vaccine Institute, Seoul, Korea. halsteads@erols.com
Mahalingam
Suresh
S
Marovich
Mary A
MA
Ubol
Sukathida
S
Mosser
David M
DM
D000818:Animals; D019067:Antibody-Dependent Enhancement; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001419:Bacteria / Q000276:immunology* / Q000472:pathogenicity; D056890:Eukaryota / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D017452:Receptors, IgG / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014780:Viruses / Q000276:immunology* / Q000472:pathogenicity
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D017452:Receptors, IgG