Helminth parasites are known to be efficient modulators of their host's immune system. To guarantee their own survival, they induce alongside the classical Th2 a strong regulatory response with high levels of anti-inflammatory
cytokines and elevated plasma levels of
IgG4. This particular antibody was shown in different models to exhibit immunosuppressive properties. How
IgG4 affects the etiopathology of
lymphatic filariasis (LF) is however not well characterized. Here we investigate the impact of plasma and affinity-purified
IgG/
IgG4 fractions from endemic normals (EN) and LF infected pathology patients (CP), asymptomatic microfilaraemic (Mf+) and amicrofilaraemic (Mf-) individuals on
IgE/IL3 activated granulocytes. The activation and degranulation states were investigated by monitoring the expression of CD63/HLADR and the release of granule contents (
neutrophil elastase (NE),
eosinophil cationic protein (ECP) and
histamine) respectively by flow cytometry and ELISA. We could show that the activation of granulocytes was inhibited in the presence of plasma from EN and Mf+ individuals whereas those of Mf- and CP presented no effect. This inhibitory capacity was impaired upon depletion of
IgG in Mf+ individuals but persisted in
IgG-depleted plasma from EN, where it strongly correlated with the expression of
IgA. In addition,
IgA-depleted fractions failed to suppress granulocyte activation. Strikingly, affinity-purified
IgG4 antibodies from EN, Mf+ and Mf- individuals bound granulocytes and inhibited activation and the release of ECP, NE and
histamine. In contrast,
IgG4 from CP could not bind granulocytes and presented no suppressive capacity. Reduction of both the affinity to, and the suppressive properties of anti-inflammatory
IgG4 on granulocytes was reached only when FcγRI and II were blocked simultaneously. These data indicate that
IgG4 antibodies from Mf+, Mf- and EN, in contrast to those of CP, natively exhibit FcγRI/II-dependent suppressive properties on granulocytes. Our findings suggest that quantitative and qualitative alterations in
IgG4 molecules are associated with the different clinical phenotypes in LF endemic regions.