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Date of Award

Spring 2011

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Department of Biology

Abstract

Cutaneous leishmaniasis (CL), a vector-borne infectious disease caused by protozoan parasites of the genus Leishmania, is one of the most important neglected infectious diseases worldwide. Currently, 10 million people in 82 (mostly developing) countries are infected. Those infected develop ulcerative skin lesions on exposed parts of the body, causing serious disability and permanent scarring. All mice are susceptible to infection with Leishmania major, however, the outcome of infection is different depending on the mouse strain. For example, resistant C57BL/6 mice develop lesions, which like in humans, ultimately heal. In contrast, lesions in susceptible BALB/c mice progressively worsen, ultimately resulting in mortality. Resistance or susceptibility to Leishmania parasites is largely dependent on whether the host’s CD4+ T cells develop into Th1 or Th2 effector cells, respectively. Resistant Th1 responses are typically driven by cytokines like interleukin (IL)-12 and interferon-which promotes healing and parasite clearance. In contrast, susceptible Th2 responses are marked by elevated IL-4 production which inactivates the mechanisms of effective parasite clearance and promotes disease progression through an ineffective, antibody-dominated humoral response. IL-3 is a cytokine which promotes hematopoiesis and has the ability to act on numerous cell lineages. In particular, IL-3 appears to have specialized functions in regards to the activation of basophils. For example, IL-3 has been shown to be indispensable for increases in basophil numbers in response to certain infections. Moreover, IL-3 has been shown to increase the functional ability of basophils as IL-3-stimulated basophils are shown to secrete higher levels of IL-4. IL-3 is primarily secreted by activated CD4+ effector T cells, the same cells which are so influential in determining resistance and susceptibility to CL. However, the role of IL 3 during the response to CL remains largely unknown. In the present study we show that infected mice genetically deficient in IL-3 (IL-3 -/- mice) develop smaller lesions, have a lower parasite burdens, and express lower levels of B cells in draining lymph nodes as compared to infected IL-3 +/+ mice. These data suggest IL-3 promotes susceptibility to Leishmania infection and may play an important role in the development of a Th2 immune response characteristic of susceptible BALB/c mice.

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