Epithelial Homelessness: An Atypical form of Anoikis Triggered by Leishmania Interaction with Epithelial Cells

Abstract

Aim: Leishmaniasis is characterized by a spectrum of diseases with two main clinical forms, cutaneous and visceral, caused by Leishmania tropica and Leishmania donovani, respectively. Studying Leishmania‘s interaction with the epithelial barrier at the initial site of a bite is crucial to understanding the establishment of the disease. Materials & methods: To discern parasite–host epithelial interaction, we developed in vitro cellular models involving co-cultures of Leishmania and MDCK epithelial cells. Results: Both L. donovani–MDCK and L. tropica–MDCK co-culture models demonstrated a phenomenon known as atypical anoikis apoptosis, typically identified by distinctive ‘flipping in’ of cell membranes and disordered cytoskeletal frameworks. Conclusion: This study bridges the gap in the fundamental understanding of the intricate latticework involving vector–Leishmania–host and may inform drug development strategies.

Plain language summary

Small parasites called Leishmania are passed to humans through the bites of sandflies. These parasites cause three deadly forms of disease: one that affects the organs, one that causes skin lesions and one that affects organ linings. This study looked at how Leishmania parasites behave when they enter through the skin. We found that when the parasites were in contact with cells, the cells changed their shape and lost contact with neighboring cells. This led to a type of cell death known as anoikis, a Greek term meaning ‘homelessness’.

Tweetable abstract

This study mimicked host–parasite interactions of Leishmania with the host epithelium, revealing a novel phenomenon known as atypical anoikis apoptosis.

Keywords::

• atypical anoikis apoptosis
• epithelial cells
• host–parasite interaction
• L. donovani
• Leishmania
• L. tropica
• visceral leishmaniasis

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fmb-2023-0004

Author contributions

S Singh and S Pati conceptualized, designed and planned the study and aided in implementation, investigation and writing (original draft and review). A Chakrabarti and R Bansal contributed equally to performing experiments and plotting and analyzing data. A Chakrabarti, R Bansal and S Pati wrote the original draft and reviewed the manuscript. A Mondal and P Upadhyay contributed in confocal imaging and live-cell imaging experiments. A Gupta, P Verma and S Garg performed formal analysis and aided in preparation of the initial draft.

Acknowledgments

The authors thank the Jawaharlal Nehru University Advanced Instrumentation Research Facility for providing the Dako MoFlo™ flow cytometer and cell sorter (Beckman Coulter, CA, USA) for flow cytometry experiments.

Financial disclosure

The authors acknowledge Shiv Nadar University (SNU)/ Department of Science and Technology-Fund for Improvement of S&T Infrastructure (DST-FIST) grant, (SR/FST/LS-1/2017/59[c]) for use of the confocal microscopy facility at the Department of Life Sciences (DoLS), School of Natural Sciences (SoNS), Shiv Nadar Institute of Eminence (SNIoE), Delhi National Capital Region, 201314, India. This study was supported by the Science and Engineering Research Board (DST/CSRI/2018/247 file no. IPA/2020/000007) and Drugs and Pharmaceuticals Research Program (project no. P/569/2016-1/TDT). S Pati is supported by the Cognitive Science Research Initiative program of the Department of Science and Technology (DST/CSRI/2018/247). A Chakrabarti and A Mondal are supported by Shiv Nadar Foundation PhD fellowships. R Bansal is supported by the Indian Council of Medical Research–Department of Health Research. S Garg received funding from the Council of Scientific and Industrial Research Senior Research Associateship. P Upadhyay is a University Grants Commission fellow. A Gupta received support from the Indo-Swiss Department of Biotechnology. P Verma received support from the Indian Council of Medical Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with an interest in or conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors acknowledge Shiv Nadar University (SNU)/ DDepartment of Science and Technology-Fund for Improvement of S&T Infrastructure (DST-FIST) grant, (SR/FST/LS-1/2017/59[c]) for use of the confocal microscopy facility at the Department of Life Sciences (DoLS), School of Natural Sciences (SoNS), Shiv Nadar Institute of Eminence (SNIoE), Delhi National Capital Region, 201314, India. This study was supported by the Science and Engineering Research Board (DST/CSRI/2018/247 file no. IPA/2020/000007) and Drugs and Pharmaceuticals Research Program (project no. P/569/2016-1/TDT). S Pati is supported by the Cognitive Science Research Initiative program of the Department of Science and Technology (DST/CSRI/2018/247). A Chakrabarti and A Mondal are supported by Shiv Nadar Foundation PhD fellowships. R Bansal is supported by the Indian Council of Medical Research–Department of Health Research. S Garg received funding from the Council of Scientific and Industrial Research Senior Research Associateship. P Upadhyay is a University Grants Commission fellow. A Gupta received support from the Indo-Swiss Department of Biotechnology. P Verma received support from the Indian Council of Medical Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.