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Resistance to Leishmania major and most intracellular pathogens is usually associated with a strong T cell-mediated immunity, particularly a CD4(+) Th1 response. Mice with an inactivating knock-in mutation in the p110delta isoform of PI3K (referred to as p110delta(D910A)) show severely impaired T cell responses. Because a strong T cell response is thought(More)
The objective of this study was to develop a short-term experimental infection model for Mycobacterium avium subsp. paratuberculosis (MAP) in cattle, using small oral doses of organisms. Specifically, the effect of dose size was evaluated, as well as specific tissue predilection sites for recovery of MAP. Oral doses as low as 1.5 x 10(6) CFU reliably(More)
Leishmaniases are emerging as an important disease in human immunodeficiency virus (HIV)-infected persons living in several sub-tropical and tropical regions around the world, including the Mediterranean. The HIV/AIDS pandemic is spreading at an alarming rate in Africa and the Indian subcontinent, areas with very high prevalence of leishmaniases. The spread(More)
Infection with Leishmania major induces a protective immune response and long-term resistance to reinfection, which is thought to depend upon persistent parasites. Here we demonstrate that although effector CD4(+) T cells are lost in the absence of parasites, central memory CD4(+) T cells are maintained. Upon secondary infection, these central memory T(More)
The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast,(More)
Long-term immunity to Leishmania may require the continued presence of parasites, but previous attempts to create attenuated parasites that persist without causing disease have had limited success. Since Leishmania major mutants that lack lipophosphoglycan and other secreted phosphoglycans, termed lpg2-, persist indefinitely in infected mice without(More)
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(More)
Leishmania major infections induce the development of a CD4(+) T-helper 1 (Th1) response that not only controls the primary infection but also results in life-long immunity to reinfection. How that immunity is maintained is unknown, although because of the existence of infection-induced immunity, there has been an assumption that the development of a(More)
Despite a plethora of publications on the murine model of cutaneous leishmaniasis and their contribution to our understanding of the factors that regulate the development of CD4+ T cell immunity in vivo, there is still no effective vaccine against the human disease. While recovery from natural or experimental infection with Leishmania major, the causative(More)
Experimental infection of BALB/c mice with a high number of Leishmania major parasites results in a predominant Th2 response and rapidly progressing, non-healing lesions. Disease can be prevented in such mice by simple therapies, such as administering neutralizing anti-IL-4 or anti-CD4 antibody prior to or around the time of infection, but not once the(More)