Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages.
M2 macrophages suppress inflammation in numerous disorders, including tumour formation, infection and obesity. However, the exact role of M2 macrophages in the context of several other diseases is still largely undefined. We here show that human M2 macrophages promote inflammation instead of suppressing inflammation on simultaneous exposure to complexed IgG (c-IgG) and TLR ligands, as occurs in the context of diseases such as rheumatoid arthritis (RA). c-IgG-TLR ligand co-stimulation of M2 macrophages selectively amplifies production of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and promotes Th17 responses, which all play a critical role in RA pathology. Induction of pro-inflammatory cytokines on c-IgG co-stimulation mainly depends on Fc gamma receptor IIa (FcγRIIa), which selectively amplifies cytokine gene transcription and induces caspase-1 activation. These data indicate that FcγR-TLR cross-talk may be targeted for treatment to attenuate inflammation in RA, by restoring the anti-inflammatory function of M2 macrophages.
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Lisa T C
LT
Vogelpoel
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Ivo S
IS
Hansen
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1006 AN Amsterdam, The Netherlands.
Theo
T
Rispens
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Femke J M
FJ
Muller
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Toni M M
TM
van Capel
Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Maureen C
MC
Turina
1] Immunaffect B.V., 1404 AK Bussum, The Netherlands [2] Department of Molecular Cell Biology and Immunology, Free University Medical Center, 1007 MB Amsterdam, The Netherlands.
Joost B
JB
Vos
Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Dominique L P
DL
Baeten
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Martien L
ML
Kapsenberg
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Esther C
EC
de Jong
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Jeroen
J
den Dunnen
D020170:Caspase 1 / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology*; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*; D058504:Th17 Cells / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
C080568:Fc gamma receptor IIA; D053583:Interleukin-1beta; D015850:Interleukin-6; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D020170:Caspase 1