Immunological characteristics of experimental murine infection with Leishmania (Leishmania) amazonensis (original) (raw)
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Immunopathological Studies of Leishmania amazonensis Infection in Resistant and in Susceptible Mice
Journal of Infectious Diseases, 2010
Leishmania amazonensis infection was studied in mice to evaluate the evolution of leishmaniasis. The association of different methods, such as lesion kinetics, limiting dilution analysis, and immunohistochemistry, established different levels of susceptibility and resistance. Mice were arranged in 3 groups: susceptible (C57BL/ 10 and CBA), relatively resistant (DBA/2), and resistant (C3H.He). The histopathological analysis of primary lesions and draining lymph nodes showed a predominance of eosinophils and mast cells in the initial phase of infection in all mice. However, the most susceptible mice presented a greater number of amastigotes and higher tissue damage. The immunoglobulin analysis showed that susceptible mice produced high levels of antibodies, whereas resistant and relatively resistant mice exhibited low production of antibodies.
Experimental Parasitology, 1992
amazonensis infection: A comparison of in vivo leishmanicidal mechanisms between immunized and naive infected BALBlc mice. Experimental Parasitology 74, 169-176. In vitro studies have shown that both macrophage activation and destruction of parasitized macrophages lead to leishmania destruction. The relative role played by such mechanisms in vivo have not been properly evaluated. We took advantage of the model of intravenous immunization with solubilized leishmanial antigen which renders partially resistant the otherwise highly susceptible BALB/c mice to address this issue avoiding the interference of different genetic backgrounds. Leishmania destruction occurred in three situations: destruction of the parasitized macrophage, which were in close contact with lymphocytes or eosinophils; extracellular damage, always surrounded by small foci of granulocytes; and parasite damage inside activated macrophages. Destruction of the parasitized macrophages was frequently seen in immunized and protected animals. Our observations suggest that destruction of parasite-loaded macrophages is an important mechanism of host protection in experimental cutaneous leishmaniasis. 0 19% Academic PESS, IX.
Study of Leishmania pathogenesis in mice: experimental considerations
Parasites & Vectors, 2016
Although leishmaniases are endemic in 98 countries, they are still considered neglected tropical diseases. Leishmaniases are characterized by the emergence of new virulent and asymptomatic strains of Leishmania spp. and, as a consequence, by a very diverse clinical spectrum. To fight more efficiently these parasites, the mechanisms of host defense and of parasite virulence need to be thoroughly investigated. To this aim, animal models are widely used. However, the results obtained with these models are influenced by several experimental parameters, such as the mouse genetic background, parasite genotype, inoculation route/infection site, parasite dose and phlebotome saliva. In this review, we propose an update on their influence in the two main clinical forms of the disease: cutaneous and visceral leishmaniases.
Microbes and Infection, 2000
Most experimental studies on leishmaniasis compare two different inbred strains of mice that are resistant or susceptible to one species of Leishmania. In the present study we characterized some cytokines and nitric oxide production as well as histological changes related to resistance and susceptibility in isogenic CBA mice infected with Leishmania major or Leishmania amazonensis. CBA mice are capable of controlling infection with L. major, but they succumb to infection with L. amazonensis. Cells from susceptible L. amazonensis-infected CBA mice produced interleukin (IL)-4 and IL-10 but no interferon (IFN)-γ. On the other hand, resistant L. major-infected CBA mice produced IFN-γ and IL-10, but IL-4 was detected only in the first week of infection. Histopathological studies showed patterns of tissue responses at the site of the infection and in the draining lymph nodes that correlated with resistance or susceptibility. Resistant mice showed a mixed inflammatory cell infiltration and granulomas in the lesions, whereas in susceptible mice only heavily parasitized macrophages were seen. Our results indicate an important role of the parasite species in determining the pattern of immune response. L. amazonensis induces a Th2-type immune response, whereas L. major induces a Th1-type response. These factors must be identified and taken into account in the strategies for the development of vaccines against leishmaniasis. The model presented here will be useful for the study of such factors.
Mechanisms of pathogenesis: differences amongst Leishmania species
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2002
One of the features of the genus Leishmania is the diversity of tropism/disease resulting from infection. With notable exceptions, the form (visceral, cutaneous, diffuse cutaneous, mucocutaneous) and severity of disease is a function of the infecting Leishmania species together with host genetics and consequent inflammatory and immune responses. It has become evident from genetic and immunological studies using the murine model that the various members of the genus Leishmania differ in aspects of their 'approach' to the host immune system. We are just beginning to appreciate the complexities of these interactions, which have import for the development of a vaccine against leishmaniasis. In this paper, what is currently understood concerning the mechanisms of leishmanial pathogenesis (based upon studies employing the murine model) is briefly summarized.
Animal Models for the Study of Leishmaniasis Immunology
Revista do Instituto de Medicina Tropical de São Paulo, 2014
Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers ("low" 1x10 2 and "high" 1x10 6 ) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.