ABSTRACT
The biological behavior of Leishmania amazonensis in the mammalian host is highly variable, resulting in local to diffuse cutaneous lesions that sometimes metastasize. Inflammation and, more specifically, CD4+ T cells have been shown to enhance metastases in mice infected with L. amazonensis, suggesting that the process may be lymphocyte mediated. However, we document, in this study, the development of multiple cutaneous metastases in C3H SCID mice infected with L. amazonensis. This shows that functional T and B cells are not required for metastases to occur.
Subject(s)
Leishmania mexicana/pathogenicity , Leishmaniasis, Cutaneous/pathology , Animals , B-Lymphocytes/immunology , Disease Models, Animal , Female , Leishmania mexicana/immunology , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Mice , Mice, Inbred C3H , Mice, SCID , T-Lymphocytes/immunologyABSTRACT
Dendritic cells have been shown to be the main antigen-presenting cells in vitro and in vivo, playing a pivotal role in the induction of both tolerance and immunity. Dendritic cells from humans and mice have been extensively studied and dendritic cell-based vaccines have been shown to be effective in the prevention and treatment of infectious, allergic and neoplastic diseases. Studies of dendritic cells of domestic animal origin are becoming available and confirm a role for these cells in the pathogenesis of a variety of animal diseases, suggesting that dendritic cells could be used as adjuvants for prophylactic and therapeutic strategies in veterinary medicine.
Subject(s)
Adjuvants, Immunologic/physiology , Dendritic Cells/cytology , Dendritic Cells/physiology , Immunotherapy/veterinary , Animals , Cancer Vaccines/therapeutic use , Humans , Immunotherapy/methods , Vaccines/therapeutic useABSTRACT
The granulomatous enteric lesions of cattle with Johne's disease are composed of infected macrophages, and grow by accumulation, re-infection, and expansion of macrophage populations in the intestinal wall. We have examined the growth of bacteria in macrophages to define characteristics of intracellular trafficking for exocytosis, replication, and antigen presentation. Using immunocytochemical markers for light, confocal and electron microscopy, we have examined potential pathway tropisms using data for bacterial attachment, phagosomal acidification, phagolysosomal degradation and apoptosis. Our hypotheses are that pathogenic/wild-type strains block phagosomal acidification so that the phagosome fails to obtain markers of the late phagosome and phagolysosome, and this leads to the replication pathway within bacteriophorous vacuoles. Non-pathogenic strains appear to be processed to exocytosis, and avirulent mutant strains may be degraded and have preference of antigen processing pathways that involve transport vesicles bearing MHC II antigens. Pathogenicity in a nude mouse model of intestinal infection reveals lesion development and confirms pathway preferences of virulent strains for bacteriophorous vacuole formation.
