Enhancement of experimental cutaneous leishmaniasis by Leishmania extract: identification of a disease-associated antibody specificity (original) (raw)
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Infection and Immunity, 2011
Most inbred strains of mice, like the BALB/c strain, are susceptible to Leishmania amazonensis infections and resistant to Leishmania braziliensis infections. This parasite-related difference could result from the activity of an L. amazonensis-specific virulence factor. In agreement with this hypothesis, it is shown here that the intravenous injection of BALB/c mice with L. amazonensis amastigote extract (LaE) but not the L. braziliensis extract confers susceptibility to L. braziliensis infection. This effect was associated with high circulating levels of IgG1 anti-L. amazonensis antibodies and with an increase in interleukin-4 (IL-4) production and a decrease in gamma interferon production by draining lymph node cells. Moreover, the effect was absent in IL-4knockout mice. The biological activity in the LaE was not mediated by amphiphilic molecules and was inhibited by pretreatment of the extract with irreversible serine protease inhibitors. These findings indicate that the LaE contains a virulence-related factor that (i) enhances the Leishmania infection by promoting Th2-type immune responses, (ii) is not one of the immunomodulatory Leishmania molecules described so far, and (iii) is either a serine protease or has an effect that depends on that protease activity. In addition to being Leishmania species specific, the infection-enhancing activity was also shown to depend on the host genetic makeup, as LaE injections did not affect the susceptibility of C57BL/6 mice to L. braziliensis infection. The identification of Leishmania molecules with infection-enhancing activity could be important for the development of a vaccine, since the up-or downmodulation of the immune response against a virulence factor could well contribute to controlling the infection.
Veterinary Parasitology, 2008
The murine models of Leishmania infection are well-studied and suitable models for studying this disease, which, despite its incidence of nearly 2 million new cases worldwide per year and its prevalence of 12 million cases, has been a somewhat neglected disease. Data obtained using such models are important for a better understanding of the disease in humans due to similarities in physiology and the advantage provided by the uniform infection profile within each mouse strain. In this review, we focus on studies of experimental murine infection with Leishmania (Leishmania) amazonensis, a species that has been associated with infections exhibiting various clinical features in humans. Mainly, we point out and discuss reports on: the effects of variations of the inoculum (such as strain, site, and size) in the establishment and development of the infection; characteristics of the infection in distinct mouse strains; and, the effects and subversions of the infection on components of the host innate and adaptive immune responses. The results obtained in these studies show that L. (L.) amazonensis infection in mice presents some unique features and immunoregulatory mechanisms, making it an interesting model for obtaining further knowledge of potential drugs targets and immunotherapy in Leishmania infection. #
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.
Revista da Associação Médica Brasileira, 1999
PURPOSE. To develop an animal model for studying mucocutaneous leishmaniasis. METHODS. The hind footpad of C57Bl/6j inbred mice was experimentally infected with 10 7 Leishmania (Leishmania) amazonensis promastigote and the skin was studied through light and electron transmission microscopy and immunohistochemistry (PAP) techniques. RESULTS. There were morphological evidences of cellular immune mechanisms and hypersensitivity reaction after eight weeks of infection and metas
Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis
Infection and immunity, 1995
In the search for a leishmaniasis vaccine, extensive studies have been carried out with promastigote (insect stage) molecules. Information in this regard on amastigote (mammalian host stage) molecules is limited. To investigate host immune responses to Leishmania amastigote antigens, we purified three stage-specific antigens (A2, P4, and P8) from in vitro-cultivated amastigotes of Leishmania pifanoi by using immunoaffinity chromatography. We found that with Corynebacterium parvum as an adjuvant, three intraperitoneal injections of 5 micrograms of P4 or P8 antigen provided partial to complete protection of BALB/c mice challenged with 10(5) to 10(7) L. pifanoi promastigotes. These immunized mice developed significantly smaller or no lesions and exhibited a 39- to 1.6 x 10(5)-fold reduction of lesion parasite burden after 15 to 20 weeks of infection. In addition, P8 immunization resulted in complete protection against L. amazonensis infection of CBA/J mice and partial protection of BAL...
BMC Research Notes, 2014
Background: It has been reported that repeated intravenous injections of a relatively large amount of Leishmania amazonensis amastigote extract (LaE) in BALB/c mice exacerbates the infection of these mice by Leishmania braziliensis. The identification of the extract active principle(s) through physicochemical purification often involves dilution and losses of protein in the course of successive purification procedures. The large amount of the extract required to induce the phenomenon, therefore, hinders the carrying out of experiments aimed at identifying the active molecule(s) through extract purification. In the present work, a dose-response experiment was done to find out if smaller amounts of LaE than that necessary to be used by the intravenous route would reproduce the phenomenon when injected by the intradermal route. In addition, it was also investigated whether a Leishmania braziliensis amastigote extract (LbE) would exert the same effect and whether the effect would occur in C57BL/6 mice. Results: It was found that a single injection of either LaE or LbE containing 5 μg of protein was capable of enhancing the infection in BALB/c but not in C57BL/6 mice. In addition, it was observed that the largest tested doses of LbE (containing 30 and 180 μg of protein) failed to enhance the infection by L. braziliensis, whereas all doses of LaE enhanced equally that infection. Conclusions: Those results indicate the possible existence in LbE, and not in LaE, of molecules that interfere with the extract infection-enhancing activity when it is injected in large amounts, and that the inoculation of Leishmania extracts through the intravenous and intradermal routes potentiate the infection by L. braziliensis through the same mechanism.