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Leishmania major: effect of infectious dose on T cell subset development in BALB/c mice
1Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland 20892, USA.
Abstract:
Leishmania major, the causative agent of cutaneous leishmaniasis in humans, causes either a local cutaneous lesion or a fatal, disseminated infection in different strains of mice. It has been well established that the BALB/c strain of mice is extremely susceptible to L. major infection, due to the preferential development of Th2 responses. It has also been shown, however, that these mice have the potential to develop protective Th1 responses under appropriate conditions. In this paper we confirm earlier reports that BALB/c mice are capable of developing immunity when challenged with low doses of L. major and show that this is dependent on the induction of a Th1 response which can be manipulated with anti-cytokine antibodies in the same way as more conventional experimental infections. Moreover, our data indicate that the development of immunity or susceptibility to L. major in the BALB/c mouse may reflect factors specific to infection such as persistance of the pathogen, infection of APC, or relative cytokine levels rather than simple antigen load, a finding which may be of general significance in infectious disease.
Insights
BALB/c mice can develop immunity to Leishmania major infection by mounting a protective Th1 response. This immunity is achievable even in susceptible strains, suggesting infection-specific factors influence disease outcome.
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- Leishmania major causes cutaneous leishmaniasis, with BALB/c mice exhibiting high susceptibility due to Th2 responses.
- BALB/c mice possess the potential for protective Th1 responses under specific conditions.
Purpose of the Study:
- To confirm BALB/c mice can develop immunity to Leishmania major with low-dose challenge.
- To investigate the role of Th1 responses in Leishmania major immunity in BALB/c mice.
- To explore factors beyond antigen load influencing Leishmania major infection outcomes.
Main Methods:
- Challenging BALB/c mice with low doses of Leishmania major.
- Manipulating Th1 responses using anti-cytokine antibodies.
- Analyzing immune responses and infection outcomes.
Main Results:
- BALB/c mice developed immunity when challenged with low doses of Leishmania major.
- This immunity was dependent on the induction of a Th1 response.
- Immunity or susceptibility may depend on pathogen persistence, APC infection, or cytokine levels, not just antigen load.
Conclusions:
- Leishmania major immunity in BALB/c mice is achievable and Th1-dependent.
- Factors like pathogen persistence and cytokine balance are critical in determining infection outcomes.
- Findings have broader implications for understanding infectious disease dynamics.