Unveiling <i>Taenia solium</i> kinome profile and its potential for new therapeutic targets

Arora, Naina; Raj, Anand; Anjum, Farhan; Kaur, Rimanpreet; Rawat, Suraj Singh; Kumar, Rajiv; Tripathi, Shweta; Singh, Gagandeep; Prasad, Amit

doi:10.1080/14789450.2020.1719835

Cited by 7 publications

(8 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deciphering the EV proteins make‐up is crucial to understand their effect and way of interaction with host cells and several studies previously investigated the proteomic content of helminth‐derived EV such as T. muris , A. suum , and so forth (Arora et al., 2020 ; Eichenberger et al., 2018 ; Hansen et al., 2019 ; Zhang et al., 2018 ). Tetraspanins are present in the EV membranes and are consistently reported in EV helminths‐derived EV (Sanchez‐Lopez et al., 2023 ; Zakeri et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, upon the death of the parasite, it releases a complex mixture of antigenic components into its surrounding, mediating the infiltration of different immune cells, promoting a significant increase in the immune response and heightened intracranial pressure which can lead to an episode of seizures (Garcia et al., 2014 ). Our earlier study had reported that parasite's secretome had a blend of both pro‐inflammatory as well as anti‐inflammatory proteins and is a major mediator of immune modulation in the host (Arora et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Rawat,

Keshri,

Arora

et al. 2024

J of Extracellular Vesicle

Self Cite

View full text Add to dashboard Cite

The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto‐lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV‐treated macrophages. Due to this, both macro‐autophagy and caspase‐linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT–mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV‐mediated immune suppression revealed that the EV can protect the mice from DSS‐induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Rawat,

Keshri,

Arora

et al. 2024

J of Extracellular Vesicle

Self Cite

View full text Add to dashboard Cite

show abstract

“…According to studies, certain constituents of Taenia solium can potentially interact with cancer cells and possibly exert anticancer effects (Arora et al, 2020;García-Gutiérrez et al, 2020;Plata and Castañeda, 2020). Schcolnik-Cabrera 2020 evaluated the anticancer activities of recombinant T. solium calreticulin (rTsCRT) by treating tumor cells at various concentrations (Schcolnik-Cabrera et al, 2020).…”

Section: Taenia Soliummentioning

confidence: 99%

Using Helminths to Fight Cancer: An Innovative Approach

Ameli,

Masoumi,

Kerachi

et al. 2023

WVJ

View full text Add to dashboard Cite

As an alternative treatment in cancer therapy, there has been a growing interest in using helminths, such as Trichinella spiralis (T. spiralis), Echinococcus granulosus (E. granulosus), Toxocara canis (T. canis), and Taenia solium (T. solium). This study aimed to investigate the antigens and mechanisms that contribute to the anticancer properties of helminths, providing insights into how helminths may be used as a new and innovative treatment modality for cancer. The current review analyzed preclinical and clinical studies published between 2000 and 2023. The present study sought to obtain information on helminths, such as E. granulosus, T. spiralis, T. canis, and T. solium, to treat cancers of the breast, pancreas, melanoma, and leukemia by exploring databases, such as PubMed, Google Scholar, and Scopus. Studies focusing on helminth therapy against particular cancer types for in vitro and animal models were included. Several studies have shown the possibility of inhibiting breast, colon, melanoma, and leukemia tumor growth, inducing apoptosis, and modulating the tumor microenvironment with E. granulosus, T. spiralis, T. canis, and T. solium based on in vitro and animal models studies. Some studies have indicated that helminth therapy can improve survival rates, reduce tumor growth, and stimulate the immune system in cancer patients. A potential improvement in treatment outcomes can be used for combination therapies, such as antigen selection, immune profiling, and individualized approaches based on helminth therapy. Helminth therapy is an additional option for cancer treatment, emphasizing T. spiralis, E. granulosus, T. canis, and T. solium. These helminth antigens could modulate immune responses and directly cause cytotoxicity in cancer cells.

show abstract

“…These reports had helped us in our earlier studies where we had identified the different proteins present in T . solium secretome and kinome associated with different cellular processes like cell proliferation, cell adhesion, migration, and maturation [ 23 – 24 ]. This also established ESPs as a significant source of “immunogenic proteins” due to their availability to be processed and recognized by the host immune system.…”

Section: Introductionmentioning

confidence: 99%

Taenia solium excretory secretory proteins (ESPs) suppresses TLR4/AKT mediated ROS formation in human macrophages via hsa-miR-125

Arora,

Keshri,

Kaur

et al. 2023

PLoS Negl Trop Dis

Self Cite

View full text Add to dashboard Cite

Background Helminth infections are a global health menace affecting 24% of the world population. They continue to increase global disease burden as their unclear pathology imposes serious challenges to patient management. Neurocysticercosis is classified as neglected tropical disease and is caused by larvae of helminthic cestode Taenia solium. The larvae infect humans and localize in central nervous system and cause NCC; a leading etiological agent of acquired epilepsy in the developing world. The parasite has an intricate antigenic make-up and causes active immune suppression in the residing host. It communicates with the host via its secretome which is complex mixture of proteins also called excretory secretory products (ESPs). Understanding the ESPs interaction with host can identify therapeutic intervention hot spots. In our research, we studied the effect of T. solium ESPs on human macrophages and investigated the post-translation switch involved in its immunopathogenesis. Methodology T. solium cysts were cultured in vitro to get ESPs and used for treating human macrophages. These macrophages were studied for cellular signaling and miR expression and quantification at transcript and protein level. Conclusion We found that T. solium cyst ESPs treatment to human macrophages leads to activation of Th2 immune response. A complex cytokine expression by macrophages was also observed with both Th1 and Th2 cytokines in milieu. But, at the same time ESPs modulated the macrophage function by altering the host miR expression as seen with altered ROS activity, apoptosis and phagocytosis. This leads to activated yet compromised functional macrophages, which provides a niche to support parasite survival. Thus T. solium secretome induces Th2 phenomenon in macrophages which may promote parasite’s survival and delay their recognition by host immune system.

show abstract

Unveiling Taenia solium kinome profile and its potential for new therapeutic targets

Cited by 7 publications

References 63 publications

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Using Helminths to Fight Cancer: An Innovative Approach

Taenia solium excretory secretory proteins (ESPs) suppresses TLR4/AKT mediated ROS formation in human macrophages via hsa-miR-125

Contact Info

Product

Resources

About