HUMAN MONOCYTE INFECTION BY LEISHMANIA (VIANNIA) PANAMENSIS - ROLE OFCOMPLEMENT RECEPTORS AND CORRELATION OF SUSCEPTIBILITY IN-VITRO WITH CLINICAL PHENOTYPE

Peripheral blood monocytes (PBMs) from healthy individuals who had exp erienced distinctive clinical outcomes after natural infection with Le ishmania (Viannia) were evaluated in vitro with respect to susceptibil ity to infection by stationary phase promastigotes of L. (V). panamens is. Concomitantly, the role of complement receptors (CR) CR1 and CR3 i n the attachment and entry of L. (V). panamensis into human monocytes was analyzed using mAbs to CR1 (CD35) and CR3 (CD11b) to inhibit compe titively these early events in the host-parasite interaction. Cell adh erence to fibronectin was examined to determine how modulation of CR a ctivity affected the attachment and uptake of this parasite species. T he human monocyte cell line U-937 was also evaluated and found to prov ide a reproducible control for L. (V). panamensis infection in vitro. Opsonization with fresh AB+ serum markedly enhanced uptake by both PBM s and U-937 cells, and the fluid phase blocking of CR1 and CR3 resulte d in partial inhibition of attachment and/or internalization. Uptake r ather than attachment was abrogated by antireceptor antibodies in PBMs from previously infected individuals, whereas attachment was diminish ed in PBMs from unexposed controls. Adherence of PBMs to fibronectin r esulted in decreased infection. PBMs from persons who had experienced chronic disease 5 to 8.4 yr before these studies were significantly mo re susceptible to in vitro infection by L. (V). panamensis than PBMs f rom asymptomatically infected or control individuals based on the perc entage of cells infected, the number of parasites per cell, and viabil ity of intracellular parasites at 48 h postinfection. Neither blocking of CR nor modulation by fibronectin altered the pattern of susceptibi lity of PBMs from the different clinical groups. These findings provid e evidence for the participation of CR in the infection of human monoc ytes by L. (V). panamensis and demonstrate a correlation between clini cal phenotype and in vitro infection of PBMs cultured in the presence of autologous plasma before experimental infection.