The Route of Leishmania tropica Infection Determines Disease Outcome and Protection against Leishmania major in BALB/c Mice

Abstract

Leishmania tropica is one of the causative agents of leishmaniasis in humans. Routes of infection have been reported to be an important variable for some species of Leishmania parasites. The role of this variable is not clear for L. tropica infection. The aim of this study was to explore the effects of route of L. tropica infection on the disease outcome and immunologic parameters in BALB/c mice. Two routes were used; subcutaneous in the footpad and intradermal in the ear. Mice were challenged by Leishmani major, after establishment of the L. tropica infection, to evaluate the level of protective immunity. Immune responses were assayed at week 1 and week 4 after challenge. The subcutaneous route in the footpad in comparison to the intradermal route in the ear induced significantly more protective immunity against L. major challenge, including higher delayed-type hypersensitivity responses, more rapid lesion resolution, lower parasite loads, and lower levels of IL-10. Our data showed that the route of infection in BALB/c model of L. tropica infection is an important variable and should be considered in developing an appropriate experimental model for L. tropica infections.

Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

“…Our observations demonstrate that the number of parasites that establishes infection must be considered in interpreting the influence of the site of infection, as suggested previously (6). We and others have demonstrated that the relative differences in parasite load or lesion size following inoculation at different sites or with different doses of parasites can change depending on the time of analysis (1,3,7,36,48). For example, while we observed earlier control of parasite numbers in the ear than in the footpad, likely due to the earlier onset of adaptive immunity as shown here, a 10-fold-higher parasite load was maintained in the ear during chronic infection (3).…”

Visualization of Leishmania tropica Infection in BALB/c Mice by Bioluminescence Imaging

“…The results, thus, showed that the route of infection is important for parasite estimation. As reported before, the route of infection in an animal model is a very vital subject for generating suitable immunity against leishmaniasis [23] . Furthermore, the BLI method allowed the observation and measurement of transfected parasite load in the real-time of infection in infected footpad and ear.…”

The outcome of arginase activity inhibition in BALB/c mice hosting Leishmania tropica

“…8 Here, we used nor- and second, L. tropica creates a minor CL phenotype with a chronic course in BALB/c mice. 18,21 Following the prevention of ARG activity, the parasite burden declined in the dLNs of mice in nor-NOHA-Ltrop group in comparison with PBS-Ltrop group despite the fact that footpad size was not remarkably different between two groups. The ample evidence has represented that the footpad thickness is not a valid clinical measure of CL in mice.…”

“…The inhibitor was administered in minimal dose (10 μg/mouse) and distant time intervals (twice a week) to have a minimum effect to know whether this inhibitor can partially protect the Ltrop ‐infected mice through ARG activity modulation and raising the NO amount instead of urea. This study focused on L. tropica infection first because, BALB/c mice are not a susceptible animal model for L. tropica and second, L. tropica creates a minor CL phenotype with a chronic course in BALB/c mice …”