Identification of novel Leishmania major antigens that elicit IgG2a response in resistant and susceptible mice

Abstract

Experimental murine models with high, intermediate and low levels of genetically based susceptibility to Leishmania major infection reproduce almost entire spectrum of clinical manifestations of the human disease. There are increasing non-comparative studies on immune responses against isolated antigens of L. major in different murine strains. The aim of the present study was to find out whether there is an antigen that can induce protective immune response in resistant and susceptible murine strains. To do that, crude antigenic extract of procyclic and metacyclic promastigotes of L. major was prepared and subjected to SDS-PAGE electrophoresis. Western-blotting was used to search for antigen(s) capable of raising high antibody level of IgG2a versus IgG1 in the sera of both infected resistant and susceptible strains. Two novel antigens from metacyclic promastigotes of L. major (140 and 152 kDa) were potentially able to induce specific dominant IgG2a responses in BALB/c and C57BL/6 mice. The 2 antigens also reacted with IgG antibody of cutaneous leishmaniasis patients. We confirm that 140 and 152 kDa proteins of L. major promastigotes are inducing IgG production in mice and humans.

Ox40L–Ox40 pathway plays distinct roles in regulating Th2 responses but does not determine outcome of cutaneous leishmaniasis caused by Leishmania mexicana and Leishmania major

“…Although it is generally accepted that the Th2 cytokine IL-4 contributes to the generation of antigen specific IgG1 antibodies, other cytokines (Bryson et al, 2008) and parasite derived factors (Buxbaum, 2013; Mohammadi et al, 2006) have been shown to affect IgG subclass distribution. Moreover, levels of IgG1 and IgG2a antibodies do not always correlate with disease outcome (Fossati-Jimack et al, 2000).…”

Purification and biochemical characterization of two novel antigens from Leishmania major promastigotes

“…Previously, we showed that 152 and 140 kDa proteins from the L. major promastigotes were capable to induce antibodies of the IgG2a isotype in both susceptible and resistant mice (Mohammadi et al, 2006). In the present study, we made attempts to purify these 2 recently detected novel antigens from L. major pro- (Fig.…”

“…Previously we have shown that 2 novel antigens from L. major promastigotes in the late log-phase of growth are capable to induce antibodies of the IgG2a isotype in both resistant and susceptible mice (Mohammadi et al, 2006). The goal of the current study is to localize and further characterize these novel antigens.…”

“…In summary, biochemical and immunological procedures were utilized in the present study for micropreparative co-purification and partial characterization of 2 novel L. major proteins from SLA fraction. These antigens were previously found to induce an IgG2a response in mice (Mohammadi et al, 2006) and may elicit Th1 cell responses in humans. Because of relatively low expression of these proteins in L. major, cloning and expression of full length proteins or immunoreactive fragments should be used for a detailed analysis of their role in eliciting potentially protective CD4 Th1 cell responses and should ultimately contribute to the development of a defined L. major vaccine.…”

Protective effect of lectin from Synadenium carinatum on Leishmania amazonensis infection in BALB/c mice

“…In leishmaniasis, resistance and resolution of the illness have been associated with IgG2a production (Mohammadi et al, 2006) and activation of Th1 cells with secretion of IL-2 and IFN-γ. In mice, IL-4 secreted by Th2 cells induces an immunoglobulin isotype switch on B lymphocytes to IgG1 and IgE, whereas IFN-γ produced by Th1 clones increased the response of the IgG2a isotype (Stavnezer, 1996).…”