Requirement of lipophosphoglycan for intracellular survival of Leishmania donovani within human monocytes.
The function of the lipophosphoglycan of Leishmania donovani parasites was investigated in human peripheral monocytes. In contrast to wild-type L. donovani which grow in monocytes, incubation of monocytes with two variant lines of L. donovani, defective in lipophosphoglycan expression, resulted in the entry of the variant cells into the monocytes and their subsequent destruction. Passive transfer of lipophosphoglycan to the variant cells led to prolonged survival in monocytes. These results indicate that lipophosphoglycan is required by the parasite for intracellular survival. To investigate one possible protective role of the glycoconjugate, preincubation of monocytes with a suspension of lipophosphoglycan and subsequent treatment of the cells with PMA or opsonized zymosan resulted in an attenuation of the oxidative burst; the attenuation effect was concentration dependent on the glycoconjugate and independent of preincubation time. Moreover, hydrophobic beads, coated with lipophosphoglycan, were phagocytized by monocytes and found to inhibit oxygen consumption in monocytes activated with PMA. These results suggest a possible relationship between the absence of lipophosphoglycan in the variant parasites and their inability to survive within monocytes. Although the precise molecular basis remains to be elucidated, the ability of lipophosphoglycan to impair the microbial oxidative response may be a contributing factor in its requirement for intracellular survival.
McNeely
T B
TB
Department of Biochemistry, University of Kentucky Medical Center, Lexington 40536.
Turco
S J
SJ
D000818:Animals; D006028:Glycosphingolipids / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007893:Leishmania donovani / Q000254:growth & development* / Q000472:pathogenicity; D009000:Monocytes / Q000469:parasitology*; D010101:Oxygen Consumption / Q000187:drug effects; D010587:Phagocytosis; D012276:Ricin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D006028:Glycosphingolipids; C008290:lipophosphonoglycan; D012276:Ricin; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate