Memory T cells in cutaneous leishmaniasis

Glennie, Nelson D.; Scott, Phillip

doi:10.1016/j.cellimm.2016.07.010

Cited by 36 publications

(43 citation statements)

References 66 publications

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“…With this objective in mind, prior to the challenge, we employed a co-culture system of spleen cells from the immunized animals and naïve BMDCs previously pulsed with SLA or infected with L. amazonensis metacyclic promastigotes. Considering that DCs play a central role in initiating a specific T-cell immune response, leading to a resistant immune phenotype in mice, humans and dogs [31,[52][53][54][55], together with the importance of memory T cells in establishing an effective long-term immunity [19,52,[56][57][58], encouraged us to use this co-culture system. Interestingly, HisAK70 DNA immunization promoted a strong antigen-specific effector Th1 cellular response 30 days post-immunization, as evidenced by higher IFN-γ/IL-10, IFN-γ/IL-4, GMCSF/IL-10 and GMCSF/IL-4 ratios, compared to results obtained in the vector and control mouse groups.…”

Section: Discussionmentioning

confidence: 99%

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

et al. 2019

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Leishmania amazonensis is the aetiological agent of a broad spectrum of leishmaniosis in South America. It can cause not only numerous cases of cutaneous leishmaniosis but also diffuse cutaneous leishmaniosis. Considering the diversity of parasite species causing different forms of the disease that coexist in the same region, it is desirable to develop a vaccine capable of eliciting cross-protection. We have previously described the use of HisAK70 DNA vaccine for immunization of mice to assess the induction of a resistant phenotype against Leishmania major and infantum infections. In this study, we extended its application in the murine model of infection by using L. amazonensis promastigotes. Our data revealed that 14 weeks post-infection, HisAK70-vaccinated mice showed key biomarkers of protection, such as higher iNOS/arginase activity, IFN-γ/IL-10, IFN-γ/IL-4, and GM-CSF/IL-10 ratios, in addition to an IgG2a-type response when compared to the control group. These findings correlated with the presentation of lower footpad swelling and parasite burdens in the immunized compared to the control mice. Overall, this study suggests that immunization with HisAK70 may be considered a suitable tool to combat leishmaniosis as it is able to induce a potent cellular immune response, which allows to control the infection caused by L. amazonensis.

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Section: Discussionmentioning

confidence: 99%

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

et al. 2019

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“…Current vaccines, including those for IAV, do not induce robust T‐cell responses . Developing strategies to induce strong T‐cell memory could improve protection against not only IAV, but also other global health threats including human immunodeficiency virus, tuberculosis, malaria and leishmaniasis against which effective vaccination is currently absent. In the case of IAV, this strategy is supported by human studies correlating more robust CD4 and CD8 T‐cell responses with improved clinical outcomes, and decades of studies in animal models .…”

Section: Introductionmentioning

confidence: 99%

Early programming and late‐acting checkpoints governing the development of CD4 T‐cell memory

Dhume

McKinstry

2018

Immunology

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CD4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD4 T-cell generation into vaccine strategies therefore offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long-term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains. A major barrier in the design of such vaccines is that the mechanisms controlling the efficiency with which memory cells form remain incompletely understood. Here, we discuss recent insights into fate decisions controlling memory generation. We focus on the importance of three general cues: interleukin-2, antigen and co-stimulatory interactions. It is increasingly clear that these signals have a powerful influence on the capacity of CD4 T cells to form memory during two distinct phases of the immune response. First, through 'programming' that occurs during initial priming, and second, through 'checkpoints' that operate later during the effector stage. These findings indicate that novel vaccine strategies must seek to optimize cognate interactions, during which interleukin-2-, antigen- and co-stimulation-dependent signals are tightly linked, well beyond initial antigen encounter to induce robust memory CD4 T cells.

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“…Generation of long‐lived immunologic memory is essential in anti‐leishmanial immunity . Ability of a leishmanial antigen to reactivate vaccination‐primed Th cells during challenge infection is necessary for protection.…”

Section: Introductionmentioning

confidence: 99%

Leishmania major adenylate kinase immunization offers partial protection to a susceptible host

Zutshi

Kumar

Sarode

et al. 2020

Parasite Immunology

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Leishmaniasis is caused by the protozoan parasite Leishmania which inflicts significant morbidity and mortality, depending upon species and disease severity. Nearly 350 million people are at risk across 75 visceral leishmaniasis (VL) endemic and 87 cutaneous leishmaniasis (CL) endemic countries. 1,2 None of the vaccination trials in the past eight decades has met with considerable success. First-generation vaccines modalities such as leishmanization failed due to lack of consistent results and difficult standardization protocols. Purified recombinant proteins such as LACK, HASPB1, cysteine proteases or peptides gave unpromising results in pre-clinical or clinical trials. 3,4 Chemotherapies against leishmaniasis have reduced efficacy due to drug resistance, toxicity and non-compliance. 5 Therefore, prophylactic vaccination appears most reliable and cost-effective preventive method. 6 However, none of the antigens and modalities tested so far has been able to achieve the desired results.Generation of long-lived immunologic memory is essential in anti-leishmanial immunity. 7 Ability of a leishmanial antigen to reactivate vaccination-primed Th cells during challenge infection is necessary for protection. As intracellular expression of a protein dictates the fate of antigen presentation, 8 abundantly expressed leishmanial proteins would have a greater chance of being presented by MHC-II inside Leishmania-infected macrophages and may contribute to subsequent life-long immunity. In addition, vaccination strategy is an important factor which significantly affects the immunogenicity of an antigen by qualitative and quantitative availability of an antigen to APC. 9 As Leishmania major adenylate kinase (LmAdeK) is highly expressed in virulent Leishmania-infected unstimulated and IFN-γ stimulated macrophages, and as heterologous prime-boost (HPB) is more immunogenic than homologous AbstractLeishmania major causes mild-to-severe cutaneous lesions resulting in significant disfigurations, if untreated. The drugs are toxic, and drug-resistance parasites are emerging. Therefore, a prophylactic vaccination is an urgent need. As no vaccine is available, we compared the genes expressed by virulent and avirulent parasites.We identify L major adenylate kinase (AdeK) as a probable vaccine candidate after a series of experimentations. We cloned the gene in mammalian pcDNA6/HisA and pet28a + vector for in vivo expression following immunization and in vitro protein expression for booster, respectively. We observed that immunization of susceptible BALB/c mice with AdeK resulted in significant protection against L major challenge infection. The protection was accompanied by increased IFN-γ producing lymphocytes and reduced IL-4, IL-17 and IL-10 secreting central and effector Th2, Th17 and Treg memory cells, respectively. These observations indicate L major AdeK as a potential vaccine candidate. K E Y W O R D Sadenylate kinase, leishmania, Th17, Th2, vaccine

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Memory T cells in cutaneous leishmaniasis

Cited by 36 publications

References 66 publications

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

Early programming and late‐acting checkpoints governing the development of CD4 T‐cell memory

Leishmania major adenylate kinase immunization offers partial protection to a susceptible host

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