Expression of infection-related genes in parasites and host during murine experimental infection with Leishmania (Leishmania) amazonensis (original) (raw)
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Th1 and Th2 immunological profile induced by cysteine proteinase in murine leishmaniasis
Parasite Immunology, 2004
This study evaluated the immune response to three synthetic peptides (pI, VMVEQVICFD; pII, VGGGLCFE; pIII, PYFLGSIMNTCHYT) from the COOH-terminal region of Leishmania amazonensis cysteine proteinases, in BALB/cand CBA-infected mice with this parasite. Only BALB/c mice, previously inoculated with pI, showed a distinct exacerbation of the lesion. Blastogenesis assays were performed with lymph node cells from the group of mice infected with L. amazonensis, but not inoculated with the peptides, and we detected lymphoproliferative responses in BALB/c and CBA mice with a 5·0× and 2·5× stimulation index, respectively. Cell phenotypes were evaluated and in both mouse strains CD8 + cells proliferated more extensively than CD4 + cells. INF-γ and nitric oxide were detected only in supernatants obtained from CBA mouse lymph node cell cultures, whereas IL-4 was detected in supernatant cultures from both strains of mice. Our results indicate a preferential stimulation of CD8 + T-cell subsets by the pI cysteine proteinase peptide and the induction of both Th1 and Th2 phenotypes during L. amazonensis infections in both BALB/c and CBA mice. We suggest that the pI peptide from the COOH-terminal region of the cysteine proteinase induces immune responses different from those elicited by the whole molecule.
PLOS Neglected Tropical Diseases, 2015
Leishmaniasis is an important disease that affects 12 million people in 88 countries, with 2 million new cases every year. Leishmania amazonensis is an important agent in Brazil, leading to clinical forms varying from localized (LCL) to diffuse cutaneous leishmaniasis (DCL). One interesting issue rarely analyzed is how host immune response affects Leishmania phenotype and virulence. Aiming to study the effect of host immune system on Leishmania proteins we compared proteomes of amastigotes isolated from BALB/c and BALB/c nude mice. The athymic nude mice may resemble patients with diffuse cutaneous leishmaniasis, considered T-cell hyposensitive or anergic to Leishmania´s antigens. This work is the first to compare modifications in amastigotes' proteomes driven by host immune response. Among the 44 differentially expressed spots, there were proteins related to oxidative/nitrosative stress and proteases. Some correspond to known Leishmania virulence factors such as OPB and tryparedoxin peroxidase. Specific isoforms of these two proteins were increased in parasites from nude mice, suggesting that T cells probably restrain their posttranslational modifications in BALB/c mice. On the other hand, an isoform of HSP70 was increased in amastigotes from BALB/c mice. We believe our study may allow identification of potential virulence factors and ways of regulating their expression.
BMC Immunology, 2011
Background Leishmania parasites have been reported to interfere and even subvert their host immune responses to enhance their chances of survival and proliferation. Experimental Leishmania infection in mice has been widely used in the identification of specific parasite virulence factors involved in the interaction with the host immune system. Cysteine-proteinase B (CPB) is an important virulence factor in parasites from the Leishmania (Leishmania) mexicana complex: it inhibits lymphocytes Th1 and/or promotes Th2 responses either through proteolytic activity or through epitopes derived from its COOH-terminal extension. In the present study we analyzed the effects of Leishmania (Leishmania) amazonensis CPB COOH-terminal extension-derived peptides on cell cultures from murine strains with distinct levels of susceptibility to infection: BALB/c, highly susceptible, and CBA, mildly resistant. Results Predicted epitopes, obtained by in silico mapping, displayed the ability to induce cell ...
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.
Vaccine, 2006
This study demonstrates that deletion of cysteine proteinase (CP) genes diminishes pathogenicity of Leishmania mexicana in non-murine experimental host models while preserving immunogenicity. Both cpb and cpa/cpb-deficient lines induced delayed disease onset, smaller lesions and lower parasite burden in hamsters. cpa/cpb-deficient L. mexicana grew more slowly as promastigotes and presented lower infectivity and growth in human mononuclear phagocytic host cells. Protection against homologous challenge comparable to that induced by infection with the virulent wild-type (WT) L. mexicana strain was achieved in the highly susceptible hamster model by immunization with 1000 cpb-deficient promastigotes. CP-deficient L. mexicana elicited significantly lower levels of Th2-associated cytokines IL-10 and TGF- than the WT in the primary lesion of hamsters. These findings support the feasibility of using genetically attenuated live Leishmania to achieve protective immunity.
Journal of Molecular Recognition, 2014
Peptides from the COOH-terminal extension of cysteine proteinase B from Leishmania (Leishmania) amazonensis (cyspep) can modulate immune responses in vertebrate hosts. With this hypothesis as base, we used the online analysis tool SYFPEITHI to predict seven epitopes from this region with potential to bind H2 proteins. We performed proliferation tests and quantified reactive T lymphocytes applying a cytometry analysis, using samples from draining lymph node of lesions from L. (L.) amazonensis-infected mice. To define reactivity of T cells, we used complexes of DimerX (H2 D b :Ig and H2 L d :Ig) and the putative epitopes. Additionally, we applied surface plasmon resonance to verify real time interactions between the putative epitopes and DimerX proteins. Five peptides induced blastogenesis in BALB/c cells, while only two presented the same property in C57BL/6 mouse cells. In addition, our data indicate the existence of CD8 + T lymphocyte populations able to recognize each tested peptide in both murine strains. We observed an overlapping of results between the peptides that induced lymphocyte proliferation and those capable of binding to the DimerX in the surface plasmon resonance assays thus indicating that using these recombinant proteins in biosensing analyses is a promising tool to study real time molecular interactions in the context of major histocompatibility complex epitopes. The data gathered in this study reinforce the hypothesis that cyspep-derived peptides are important factors in the murine host infection by L. (L.) amazonensis.
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. #