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In vivo Imaging of Transgenic Leishmania Parasites in a Live Host
Published on: July 28, 2010
Immune elimination of Leishmania major in mice: implications for immune memory, vaccination, and reactivation disease
J E Uzonna1, G Wei, D Yurkowski
1Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Abstract:
Infection of susceptible BALB/c mice with a large, moderate, or low number of Leishmania major parasites respectively results in progressive disease, the formation of substantial but stable lesions, denoted as borderline disease, and the absence of a visible lesion. Infection with a low number of parasites results over the long term in either subclinical infections or an asymptomatic state. Subclinical mice produce a predominant Th1 response and are resistant to challenge, in contrast to their asymptomatic counterparts. Statistical and other evidence suggest that the asymptomatic state can arise from a subclinical state following parasite clearance, with consequent loss of resistance. Cell transfer studies demonstrate unequivocally that immune cells from subclinical mice can protect naive mice against a pathogenic challenge and can clear the parasite, leaving the mice susceptible to a rechallenge infection. This susceptibility is associated with the disappearance of both parasite-specific effector and memory T cells from secondary lymphoid organs. These findings have implications for vaccination, maintenance of memory, and prevention of reactivation disease.
Insights
Leishmania major infection in mice leads to varying disease outcomes. Subclinical infections confer resistance, but clearance can result in susceptibility due to T cell loss, impacting vaccination strategies.
Area of Science:
- Immunology
- Parasitology
- Infectious Disease
Background:
- Leishmania major infection in BALB/c mice causes a spectrum of outcomes, from progressive disease to asymptomatic states.
- Subclinical infections are characterized by a Th1 response and resistance to reinfection, unlike asymptomatic states.
Purpose of the Study:
- To investigate the immunological basis for resistance and susceptibility following Leishmania major infection.
- To understand the long-term consequences of subclinical infections and parasite clearance on host immunity.
Main Methods:
- Infection of BALB/c mice with varying doses of Leishmania major.
- Assessment of clinical outcomes, lesion development, and immune responses (Th1).
- Cell transfer studies to evaluate protective immunity and susceptibility to rechallenge.
Main Results:
- Low-dose Leishmania major infection results in subclinical or asymptomatic states.
- Subclinical mice exhibit Th1 responses and resistance to challenge.
- Asymptomatic state may arise from subclinical infection with parasite clearance, leading to loss of resistance.
- Immune cells from subclinical mice confer protection but clearance leads to susceptibility upon rechallenge.
- Susceptibility is linked to the disappearance of parasite-specific effector and memory T cells.
Conclusions:
- Immune memory and resistance to Leishmania major are transient and dependent on the persistence of parasite-specific T cells.
- Findings have implications for developing effective vaccination strategies and preventing disease reactivation.
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