Human monocyte infection by Leishmania (Viannia) panamensis. Role of complement receptors and correlation of susceptibility in vitro with clinical phenotype.

Peripheral blood monocytes (PBMs) from healthy individuals who had experienced distinctive clinical outcomes after natural infection with Leishmania (Viannia) were evaluated in vitro with respect to susceptibility to infection by stationary phase promastigotes of L. (V). panamensis. Concomitantly, the role of complement receptors (CR) CR1 and CR3 in the attachment and entry of L. (V). panamensis into human monocytes was analyzed using mAbs to CR1 (CD35) and CR3 (CD11b) to inhibit competitively these early events in the host-parasite interaction. Cell adherence to fibronectin was examined to determine how modulation of CR activity affected the attachment and uptake of this parasite species. The human monocyte cell line U-937 was also evaluated and found to provide a reproducible control for L. (V). panamensis infection in vitro. Opsonization with fresh AB+ serum markedly enhanced uptake by both PBMs and U-937 cells, and the fluid phase blocking of CR1 and CR3 resulted in partial inhibition of attachment and/or internalization. Uptake rather than attachment was abrogated by antireceptor antibodies in PBMs from previously infected individuals, whereas attachment was diminished in PBMs from unexposed controls. Adherence of PBMs to fibronectin resulted in decreased infection. PBMs from persons who had experienced chronic disease 5 to 8.4 yr before these studies were significantly more susceptible to in vitro infection by L. (V). panamensis than PBMs from asymptomatically infected or control individuals based on the percentage of cells infected, the number of parasites per cell, and viability of intracellular parasites at 48 h postinfection. Neither blocking of CR nor modulation by fibronectin altered the pattern of susceptibility of PBMs from the different clinical groups. These findings provide evidence for the participation of CR in the infection of human monocytes by L. (V). panamensis and demonstrate a correlation between clinical phenotype and in vitro infection of PBMs cultured in the presence of autologous plasma before experimental infection.