Recombinant Leishmania Rab6 (rLdRab6) is recognized by sera from visceral leishmaniasis patients

Chauhan, Indira Singh; Shukla, Rantidev; Krishna, Shagun; Sekhri, Savita; Kaushik, Umesh; Baby, Sabitha; Pal, Chiranjib; Siddiqi, Mohammad Imran; Sundar, Shyam; Singh, Neeloo

doi:10.1016/j.exppara.2016.09.010

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…The absorbance was measured at 492 nm using a microplate photometer (Multiskan FC, Thermo Scientific, USA). The cutoff values were calculated using the receiver operating characteristic (ROC) analysis (33, 34) using the Graphpad Prism6 program and the three categories of accuracy based on AUC–ROC analysis, as described by Solano Gallego et al (33). We additionally calculated the cutoff values using the Youden index (35–37).…”

Section: Methodsmentioning

confidence: 99%

F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis

et al. 2017

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The Leishmania (Leishmania) donovani nucleoside hydrolase NH36 is the main antigen of the Leishmune® vaccine and one of the promising candidates for vaccination against visceral leishmaniasis. The antigenicity of the N-terminal (F1), the central (F2), or the C-terminal recombinant domain (F3) of NH36 was evaluated using peripheral blood mononuclear cells (PBMC) from individuals infected with L. (L.) infantum from an endemic area of visceral leishmaniasis of Spain. Both NH36 and F1 domains significantly increased the PBMC proliferation stimulation index of cured patients and infected asymptomatic individuals compared to healthy controls. Moreover, F1 induced a 19% higher proliferative response than NH36 in asymptomatic exposed subjects. In addition, in patients cured from visceral leishmaniasis, proliferation in response to NH36 and F1 was accompanied by a significant increase of IFN-γ and TNF-α secretion, which was 42–43% higher, in response to F1 than to NH36. The interleukin 17 (IL-17) secretion was stronger in asymptomatic subjects, in response to F1, as well as in cured cutaneous leishmaniasis after NH36 stimulation. While no IL-10 secretion was determined by F1, a granzyme B increase was detected in supernatants from cured patients after stimulation with either NH36 or F1. These data demonstrate that F1 is the domain of NH36 that induces a recall cellular response in individuals with acquired resistance to the infection by L. (L.) infantum. In addition, F1 and NH36 discriminated the IgG3 humoral response in patients with active visceral leishmaniasis due to L. (L.) donovani (Ethiopia) and L. (L.) infantum (Spain) from that of endemic and non-endemic area controls. NH36 showed higher reactivity with sera from L. (L.) donovani-infected individuals, indicating species specificity. We conclude that the F1 domain, previously characterized as an inducer of the Th1 and Th17 responses in cured/exposed patients infected with L. (L.) infantum chagasi, may also be involved in the generation of a protective response against L. (L.) infantum and represents a potential vaccine candidate for the control of human leishmaniasis alone, or in combination with other HLA epitopes/antigens.

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Section: Methodsmentioning

confidence: 99%

F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis

et al. 2017

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“…One of the current challenges for the VL control revolves around improving the performance of diagnostic tests for human and veterinary use. Several studies have focused on the development of more accurate serodiagnosis, through replacing CSA by recombinant proteins [ 16 , 37 – 41 ]. Until the early 1990s, the targets used in the serological tests were the crude or soluble antigens of promastigotes or amastigotes forms of Leishmania ssp., which has a high sensitivity for the detection of specific antibodies in human and canine sera, but with a very limited specificity [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

The increased presence of repetitive motifs in the KDDR-plus recombinant protein, a kinesin-derived antigen from Leishmania infantum, improves the diagnostic performance of serological tests for human and canine visceral leishmaniasis

et al. 2021

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Visceral leishmaniasis (VL) is caused by protozoa belonging to the Leishmania donovani complex and is considered the most serious and fatal form among the different types of leishmaniasis, if not early diagnosed and treated. Among the measures of disease control stand out the management of infected dogs and the early diagnosis and appropriate treatment of human cases. Several antigens have been characterized for use in the VL diagnosis, among them are the recombinant kinesin-derived antigens from L. infantum, as rK39 and rKDDR. The main difference between these antigens is the size of the non-repetitive kinesin region and the number of repetitions of the 39 amino acid degenerate motif (6.5 and 8.5 repeats in rK39 and rKDDR, respectively). This repetitive region has a high antigenicity score. To evaluate the effect of increasing the number of repeats on diagnostic performance, we designed the rKDDR-plus antigen, containing 15.3 repeats of the 39 amino acid degenerate motif, besides the absence of the non-repetitive portion from L. infantum kinesin. Its performance was evaluated by enzyme-linked immunosorbent assay (ELISA) and rapid immunochromatographic test (ICT), and compared with the kinesin-derived antigens (rKDDR and rK39). In ELISA with human sera, all recombinant antigens had a sensitivity of 98%, whereas the specificity for rKDDR-plus, rKDDR and rK39 was 100%, 96% and 71%, respectively. When evaluated canine sera, the ELISA sensitivity was 97% for all antigens, and the specificity for rKDDR-plus, rKDDR and rK39 was 98%, 91% and 83%, respectively. Evaluation of the ICT/rKDDR-plus, using human sera, showed greater diagnostic sensitivity (90%) and specificity (100%), when compared to the IT LEISH (79% and 98%, respectively), which is based on the rK39 antigen. These results suggest that the increased presence of repetitive motifs in the rKDDR-plus protein improves the diagnostic performance of serological tests by increasing the specificity and accuracy of the diagnosis.

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“…3 μg of mRNA was converted to cDNA for each sample by using Moloney murine leukemia virus (M‐MLV) reverse transcriptase (Promega) enzyme at 37°C for 1 h which was followed by 10 min of incubation at 70°C 18 . The synthesized cDNAs were subject to real‐time PCR to determine the visceral parasite burden of the infected experimental animals by the expression of L. donovani 18S rRNA by real‐time PCR in the CFX Connect, Biorad, using the iTaq™ Universal SYBR Green Supermix (Biorad), and mRNA expressions of target genes were normalized against GAPDH and represented as the relative fold change compared with the control 25 …”

Section: Methodsmentioning

confidence: 99%

Activation of neutrophils excels the therapeutic potential of Mycobacterium indicus pranii and heat‐induced promastigotes against antimony‐resistant Leishmania donovani infection

Roy,

Ghosh,

Karan

et al. 2024

Scand J Immunol

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Repurposing drugs and adjuvants is an attractive choice of present therapy that reduces the substantial costs, chances of failure, and systemic toxicity. Mycobacterium indicus pranii was originally developed as a leprosy vaccine but later has been found effective against Leishmania donovani infection. To extend our earlier study, here we reported the immunotherapeutic modulation of the splenic and circulatory neutrophils in favour of hosts as neutrophils actually serve as the pro‐parasitic portable shelter to extend the Leishmania infection specifically during the early entry into the hosts' circulation. We targeted to disrupt this early pro‐parasitic incidence by the therapeutic combination of M. indicus pranii and heat‐induced promastigotes against antimony‐resistant L. donovani infection. The combination therapy induced the functional expansion of CD11b+Ly6CintLy6Ghi neutrophils both in the post‐infected spleen, and also in the circulation of post‐treated animals followed by the immediate Leishmania infection. More importantly, the enhanced expression of MHC‐II, phagocytic uptake of the parasites by the circulatory neutrophils as well as the oxidative burst were induced that limited the chances of the very early establishment of the infection. The enhanced expression of pro‐inflammatory cytokines, like IL‐1α and TNF‐α indicated resistance to the parasite‐mediated takeover of the neutrophils, as these cytokines are critical for the activation of T cell‐mediated immunity and host‐protective responses. Additionally, the induction of essential transcription factors and cytokines for early granulocytic lineage commitment suggests that the strategy not only contributed to the peripheral activation of the neutrophils but also promoted granulopoiesis in the bone marrow.

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Recombinant Leishmania Rab6 (rLdRab6) is recognized by sera from visceral leishmaniasis patients

Cited by 10 publications

References 38 publications

F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis

F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis

The increased presence of repetitive motifs in the KDDR-plus recombinant protein, a kinesin-derived antigen from Leishmania infantum, improves the diagnostic performance of serological tests for human and canine visceral leishmaniasis

Activation of neutrophils excels the therapeutic potential of Mycobacterium indicus pranii and heat‐induced promastigotes against antimony‐resistant Leishmania donovani infection

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