THE XID DEFECT IMPARTS SUSCEPTIBILITY TO EXPERIMENTAL MURINE FILARIOSIS - ASSOCIATION WITH A LACK OF ANTIBODY AND IL-10 PRODUCTION BY B-CELLS IN RESPONSE TO PHOSPHORYLCHOLINE

The pathways conferring immunity to filarial infections are not well k nown, in part because human pathogenic filariae do not develop a full infection cycle in laboratory mice, Using the permissive infection wit h Litomosoides sigmodontis in BALB/c mice, we have shown previously th at worm development is controlled by CD4(+) T cells and is inversely c orrelated with T(h)2 cytokine production, Here we analyzed the impact of the Xid immunodeficiency on murine filariosis, comparing the course of infection with L, sigmodontis in BALB/c and B1 cell-deficient BALB .Xid mice, In BALB.Xid mice, 2-3 times more adult worms and up to 10 t imes more microfilariae compared to BALB/c were observed to develop af ter infection with infective stage 3 larvae (L3), Parasite-specific T( h)2 cytokine production by cells from the thoracic cavity, the primary location of the parasites, was diminished significantly in BALB.Xid c ompared to BALB/c mice. In addition, BALB.Xid mice displayed a signifi cantly lower production of antibodies and a cell-derived IL-10 in resp onse to bath L. sigmodontis antigen and phosphorylcholine, a molecule we found to be abundant on the surface of L3. Thus, the a cell-defect in BALB.Xid mice may account for susceptibility to murine filarial inf ection in two ways, i.e. by the lack of antibody to a dominant surface molecule of invading L3 and by less a cell-derived IL-10 resulting in lower parasite-driven T(h)2 cytokine production.