A NovelLeishmania infantumRecombinant Antigen Which Elicits Interleukin 10 Production by Peripheral Blood Mononuclear Cells of Patients with Visceral Leishmaniasis

Abstract

We report here the characterization of a novel Leishmania infantum protein termed papLe22 (22-kDa potentially aggravating protein of Leishmania). A positive clone from a cDNA library was identified by serum of a visceral leishmaniasis (VL) patient. Full-length cDNA obtained using rapid amplification of cDNA ends-PCR codes for a 22-kDa protein. In L. infantum promastigotes an endogenous nuclear protein of 14-kDa electrophoretic mobility was found by using an antiserum prepared against the fusion protein glutathione S-transferase-papLe22. Its expression was also shown in L. infantum amastigotes and in Leishmania major and Leishmania guyanensis promastigotes. VL patients' sera showed anti-papLe22 immunoglobulin M (IgM) and IgG reactivities, indicating that a primary response against the leishmanial protein papLe22 accompanied acute VL manifestations. Specific IgG levels were correlated with patients' clinical status. The presence of IgG1, IgG2, and IgG3 subclasses suggested a mixed Th1-and Th2-type response; there was no correlation between subclass reactivity and the disease course. The recombinant papLe22 specifically activated interleukin-10 production by VL patients' peripheral blood mononuclear cells collected at diagnosis and after treatment-induced cure, indicating its contribution to VL pathogenesis and concomitant immunosuppression and its potential role in the reactivation of latent parasites. As a dominant immunogen, papLe22 might be used as a vaccine component, provided that the vaccination protocol directs the response toward the Th1 pattern.

Analysis of T helper cell responses during infection with Leishmania amazonensis.

“…It has been shown that GM-CSF and TGF-␤ are involved in leukocyte recruitment in inflammatory responses, 30,31 and that they may have inhibitory effects on a macrophage's ability to kill intracellular pathogens. 10 Given that L. donovani-and L. chagasiinfected mice also lack IL-4-dominance in disease development 32,33 and that a mixed Th1/Th2 response is a characteristic feature in L. infantum-and L. braziliensis-infected patients, [34][35][36] it is important to further examine factors responsible for susceptibility of a host to these Leishmania species.…”

A novel Leishmania infantum nuclear phosphoprotein Lepp12 which stimulates IL1-beta synthesis in THP-1 transfectants

“…After screening two expression L. infantum cDNA libraries with an acute-phase VL patient serum a 214-bp lambda gt11 insert was selected and sequenced of as described previously [29]. Then, the 267-bp ORF of Lepp12 was obtained using RACE-PCR on retrotranscribed promastigote mRNA, as indicated in the Methods section [29].…”

“…Then, the 267-bp ORF of Lepp12 was obtained using RACE-PCR on retrotranscribed promastigote mRNA, as indicated in the Methods section [29]. Figure 1 shows the deduced 87 amino acid sequence of predicted molecular weight of 11.6 kDa.…”

Humoral and In Vivo Cellular Immunity against the Raw Insect-Derived Recombinant Leishmania infantum Antigens KMPII, TRYP, LACK, and papLe22 in Dogs from an Endemic Area

“…In this sense, LACK does not induce lymphoproliferation in patients cured of VL, 52 and papLe22 elicits production of IL-10 but not IFN-γ. 53 Both antigens play a prominent role in the pathogenesis of Leishmania infection in patients with different clinical presentations. 53,54 However, vaccine strategies, such as DNA or prime-boost vaccinations, which are able to induce a strong T h 1 immune response against these antigens, have proven able to obtain protection against L. infantum , probably by promoting a redirection of their T h 2 immune response to a T h 1 profile.…”

“…53 Both antigens play a prominent role in the pathogenesis of Leishmania infection in patients with different clinical presentations. 53,54 However, vaccine strategies, such as DNA or prime-boost vaccinations, which are able to induce a strong T h 1 immune response against these antigens, have proven able to obtain protection against L. infantum , probably by promoting a redirection of their T h 2 immune response to a T h 1 profile. 30,55 The lack of a standardized antigen is the main drawback of the LST.…”