NDLI: Evolution of Lesion Formation, Parasitic Load, Immune Response, and Reservoir Potential in C57BL/6 Mice following High- and Low-Dose Challenge with Leishmania major

Content Provider	PubMed Central
Author	Lira, Rosalia Doherty, Mark Modi, Govind Sacks, David
Editor	Mansfield, J. M.
Copyright Year	2000
Abstract	A model of cutaneous leishmaniasis using 102 Leishmania major metacyclic promastigotes inoculated into the footpads of genetically resistant C57BL/6 mice was studied in order to more accurately reproduce the evolution of lesion formation and the kinetics of parasite growth and immune response as they might occur in naturally exposed reservoirs and in human hosts. In contrast to the more conventional experimental model employing 106 metacyclic promastigotes, in which the rapid development of footpad lesions was associated with an increasing number of amastigotes in the site, the low-dose model revealed a remarkably “silent” phase of parasite growth, lasting approximately 6 weeks, during which peak parasitic loads were established in the absence of any overt pathology. Footpad swelling was observed after 6 weeks, coincident with the onset of parasite clearance and with production of high levels of interleukin-12 (IL-12) and gamma interferon (IFN-γ) in draining lymph nodes. Low-dose challenge of IL-12- and IFN-γ-depleted or -deficient mice provided strong evidence that the induction or expression of cellular immunity is essentially absent during the first 6 to 8 weeks of intracellular growth, since the concentration of amastigotes in the site was not enhanced compared to that for wild-type animals during this time. By monitoring the ability of infected mice to transmit parasites to vector sand flies, it was observed that following low-dose challenge, footpads without apparent lesions provided an efficient source of parasites for exposed flies and that the low-dose challenge actually extended the duration of parasite transmissibility during the course of infection.
Starting Page	5176
File Format	PDF
ISSN	10985522
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	9
Volume Number	68
Language	English
Publisher	American Society for Microbiology
Publisher Date	2000-09-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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