Leishmania (Leishmania) amazonensisinfection and dissemination in mice inoculated with stationary-phase or with purified metacyclic promastigotes

Abstract

SUMMARY: Leishmania (Leishmania) amazonensisis a protozoan of the American Continent that causes localized cutaneous leishmaniasis and, rarely, the diffuse cutaneous form of disease in humans. It has become clear in recent years that the course ofLeishmania majorinfection in the mouse model differs when low numbers of purified metacyclic forms are used as inocula in comparison with the traditionally hitherto studied infection models that used large numbers of stationary-phase (SP) promastigotes. The low-number metacyclic inocula are thought to reproduce more closely the natural infection transmitted by the vector. In the present study the course ofL. amazonensisinfection, its local and distant dissemination patterns, and parasite load were compared in susceptible BALB/c and relatively resistant C57BL/6 mice infected in the footpad with inocula of 10⁷SP-promastigotes or with 10⁴purified metacyclic forms. Longer lag-phases were observed for infection with purified metacyclics but the characteristic patterns of disease susceptibility and cytokine production for either mouse strain were similar to those observed for SP-promastigote inocula. An inoculation dose of the order of 10⁴metacyclics was required to obtain consistent infections; 10- or 100-fold lower doses resulted in variable infection rates. Characteristically,L. amazonensisinfection spread to distant organs and persisted there also in the relatively resistant C57BL/6 mice examined after 6 months of infection.