CpG-ODN class C-mediated immunostimulation and its potential against Trypanosoma evansi in equines

Manuja, Anju; Kumar, Parveen; Kumar, Rakesh; Kumar, Balvinder; Singha, Harisankar; Sharma, Ravinder; Yadav, Suresh Chandra

doi:10.1016/j.intimp.2014.07.016

Cited by 14 publications

(5 citation statements)

References 47 publications

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“…We have observed synergistic effects of T . evansi antigen and CpGs co-culture on proliferation of horse PBMC [ 24 ]. In the present study, the rabbits were inoculated with CpG-ODN C with the aim to boost the immune response and then challenged with T .…”

Section: Resultsmentioning

confidence: 99%

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CpG-ODN Class C Mediated Immunostimulation in Rabbit Model of Trypanosoma evansi Infection

Kumar

Manuja

et al. 2015

PLoS ONE

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CpG oligodeoxynucleotides (CpG-ODN) stimulate immune cells from a wide spectrum of mammalian species. Class C CpG-ODN is relatively stable and has the combined immune effects of both A and B classes of CpG-ODN. Trypanosoma evansi produces the state of immuno-suppression in the infected hosts. The current chemotherapeutic agents against this parasite are limited in number and usually associated with severe side effects. The present work aimed to determine the immunostimulatory effects of CpG-ODN class C in T. evansi infected rabbits. Rabbits inoculated with CpG C and challenged with T. evansi resulted in delayed onset of clinical signs with reduced severity in comparison to that of T. evansi infected rabbits. The treatment also enhanced humoral immune responses. Histopathological findings in liver and spleen revealed enhancement of mononuclear cell infiltration and secondary B cell follicles. These results demonstrate that CpG-ODN class C, has immunostimulatory properties in rabbit model of trypanosomosis. The use of booster doses or sustained delivery of CpG-ODN will further elucidate the prolonged CpG-ODN generated immune responses.

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Section: Resultsmentioning

confidence: 99%

“…We have observed previously that co-culturing of T . evansi antigen in horse PBMC’s with CpG A and CpG C resulted in synergistic effect in eliciting the immune response [ 24 ].The present work aimed to determine the immuno-modulatory effects of CpG-ODN class C in rabbit model of T . evansi .…”

Section: Introductionmentioning

confidence: 99%

CpG-ODN Class C Mediated Immunostimulation in Rabbit Model of Trypanosoma evansi Infection

Kumar

Manuja

et al. 2015

PLoS ONE

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“…TLR9 engagement is involved in trypanosomosis associated IFNγ induction as well as parasitemia control of T. b. rhodesiense [55]. As TLR/MyD88 signaling gives rise to VSG-specific antibody induction [56], and TLR signaling appears crucial for maintenance of B cell memory [57,58], CpG DNA has even been proposed as an adjuvant in anti-trypanosome vaccine approaches [59][60][61][62]. Finally, it is worth nothing that IgM + B1 B cells have also been shown to play an important role in malaria-associated antibody production [63] as well as M. tuberculosis associated IgM secretion [64].…”

Section: Plos Pathogensmentioning

confidence: 99%

Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis

et al. 2021

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Salivarian trypanosomes are extracellular protozoan parasites causing infections in a wide range of mammalian hosts, with Trypanosoma evansi having the widest geographic distribution, reaching territories far outside Africa and occasionally even Europe. Besides causing the animal diseases, T. evansi can cause atypical Human Trypanosomosis. The success of this parasite is attributed to its capacity to evade and disable the mammalian defense response. To unravel the latter, we applied here for the first time a scRNA-seq analysis on splenocytes from trypanosome infected mice, at two time points during infection, i.e. just after control of the first parasitemia peak (day 14) and a late chronic time point during infection (day 42). This analysis was combined with flow cytometry and ELISA, revealing that T. evansi induces prompt activation of splenic IgM+CD1d+ Marginal Zone and IgMIntIgD+ Follicular B cells, coinciding with an increase in plasma IgG2c Ab levels. Despite the absence of follicles, a rapid accumulation of Aicda+ GC-like B cells followed first parasitemia peak clearance, accompanied by the occurrence of Xbp1+ expressing CD138+ plasma B cells and Tbx21+ atypical CD11c+ memory B cells. Ablation of immature CD93+ bone marrow and Vpreb3+Ly6d+Ighm+ expressing transitional spleen B cells prevented mature peripheral B cell replenishment. Interestingly, AID-/- mice that lack the capacity to mount anti-parasite IgG responses, exhibited a superior defense level against T. evansi infections. Here, elevated natural IgMs were able to exert in vivo and in vitro trypanocidal activity. Hence, we conclude that in immune competent mice, trypanosomosis associated B cell activation and switched IgG production is rapidly induced by T. evansi, facilitating an escape from the detrimental natural IgM killing activity, and resulting in increased host susceptibility. This unique role of IgM and its anti-trypanosome activity are discussed in the context of the dilemma this causes for the future development of anti-trypanosome vaccines.

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“…Peripheral blood mononuclear cells (PBMCs) of the Marwari horse were separated by density gradient centrifugation on histopaque (Sigma, St Louis, MO, USA) as described previously [ 15 ]. The viable cells (1 × 10 7 ) were counted by an automatic cell counter (Invitrogen, Waltham, MA, USA), and re-suspended at 10 7 cells per mL in EMEM (supplemented with 10% fetal bovine serum, 50 µg/mL ‘streptomycin sulfate, 10 µg/mL gentamicin sulfate, 2 mM L-glutamine and 50 µM 2-mercaptoethanol’.…”

Section: Methodsmentioning

confidence: 99%

Nanoformulation of a Trypanocidal Drug Isometamidium Chloride Ameliorates the Apurinic-Apyrimidinic DNA Sites/Genotoxic Effects in Horse Blood Cells

Singh

Kumar

Dilbaghi

et al. 2023

JoX

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Isometamidium chloride (ISM) is a trypanocide for the prophylactic and therapeutic use against vector-borne animal trypanosomosis (mainly Surra caused by Trypanosoma evansi) and African animal trypanosomosis caused by T. congolense/T. vivax/T. brucei). ISM was found to be an efficient trypanocide for therapeutic/prophylactic use against trypanosomosis; however, it produces some local and systemic detrimental effects in animals. We synthesized isometamidium chloride-loaded alginate gum acacia nanoformulation (ISM SANPS) to lessen the detrimental side effects of isometamidium chloride (ISM) while treating trypanosomal diseases. We intended to determine the cytocompatibility/toxicity, and DNA deterioration/chromosomal structural or number changes (genotoxicity) of ISM SANPs using mammalian cells in a concentration-dependent manner. Apurinic/apyrimidinic (AP) sites are one of the major types of DNA lesions formed during base excision and repair of oxidized, deaminated, or alkylated bases. The intensity of the cellular AP site is an excellent marker of the deterioration of DNA quality. We thought it pertinent to quantify the AP sites in ISM SANPs-treated cells. Our investigations established a dose-dependent cyto-compatibility or toxicity and DNA impairment (genotoxicity) in ISM SANPs-treated horse peripheral blood mononuclear cells. ISM SANPs were biocompatible at various concentrations tested on the mammalian cells.

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CpG-ODN class C-mediated immunostimulation and its potential against Trypanosoma evansi in equines

Cited by 14 publications

References 47 publications

CpG-ODN Class C Mediated Immunostimulation in Rabbit Model of Trypanosoma evansi Infection

CpG-ODN Class C Mediated Immunostimulation in Rabbit Model of Trypanosoma evansi Infection

Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis

Nanoformulation of a Trypanocidal Drug Isometamidium Chloride Ameliorates the Apurinic-Apyrimidinic DNA Sites/Genotoxic Effects in Horse Blood Cells

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