Publications by authors named "Roman Sarkar"

3 Publications

  • Page 1 of 1

A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells.

Front Immunol 2021 12;12:630307. Epub 2021 Apr 12.

Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India.

The study was aimed at developing an accessible laboratory animal model to elucidate protective and pathological roles of immune mediators during Peste des petits ruminants virus (PPRV) infection. It is because of the critical roles of type I IFNs in anti-viral defense, we assessed the susceptibility of IFN receptor knock out (IFNR KO) mice to PPRV infection. IFNR KO mice were exceedingly susceptible to the infection but WT animals efficiently controlled PPRV. Accordingly, the PPRV infected IFNR KO mice gradually reduced their body weights and succumbed to the infection within 10 days irrespective of the dose and route of infection. The lower infecting doses predominantly induced immunopathological lesions. The viral antigens as well as the replicating PPRV were abundantly present in most of the critical organs such as brain, lungs, heart and kidneys of IFNR KO mice infected with high dose of the virus. Neutrophils and macrophages transported the replicating virus to central nervous system (CNS) and contributed to pathology while the elevated NK and T cell responses directly correlated with the resolution of PPRV infection in WT animals. Using an array of fluorescently labeled H-2K tetramers, we discovered four immunogenic epitopes of PPRV. The PPRV-peptides interacted well with H-2K in acellular and cellular assay as well as expanded the virus-specific CD8 T cells in immunized or infected mice. Adoptively transferred CD8 T cells helped control PPRV in infected mice. Our study therefore established and employed a mouse model for investigating the pathogenesis of PPRV. The model could be useful for elucidating the contribution of immune cells in disease progression as well as to test anti-viral agents.
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http://dx.doi.org/10.3389/fimmu.2021.630307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072281PMC
September 2021

An inquiry-based approach in large undergraduate labs: Learning, by doing it the "wrong" way.

Biochem Mol Biol Educ 2020 05 3;48(3):227-235. Epub 2020 Jan 3.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Sahibzada Ajit Singh Nagar, Punjab, India.

Undergraduate laboratory courses, owing to their larger sizes and shorter time slots, are often conducted in highly structured modes. However, this approach is known to interfere with students' engagement in the experiments. To enhance students' engagement, we propose an alternative mode of running laboratory courses by creating some "disorder" in a previously adopted structure. After performing an experiment in the right way, the students were asked to repeat the experiment but with a variation at certain steps leading to the experiment being done the "wrong" way. Although this approach led to fewer experiments being conducted in a semester, it significantly enhanced the students' involvement. This was also reflected in the students' feedback. The majority of students preferred repeating an experiment with a variant protocol than performing a new experiment. Although we have tested this inquiry-based approach only for an undergraduate laboratory course in molecular biology, we believe such an approach could also be extended to undergraduate laboratory courses of other subjects.
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http://dx.doi.org/10.1002/bmb.21331DOI Listing
May 2020

Myeloid-Derived Suppressor Cells Confer Infectious Tolerance to Dampen Virus-Induced Tissue Immunoinflammation.

J Immunol 2019 09 22;203(5):1325-1337. Epub 2019 Jul 22.

Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, Punjab 140306, India

In this study, we investigated the response of myeloid-derived suppressor cells (MDSCs) during the pathogenesis of an immunoblinding disease of the cornea caused by HSV type 1 infection. We also measured the anti-inflammatory potential of in vitro-differentiated MDSCs in dampening herpetic stromal keratitis resulting from primary ocular HSV1 infection in mice. In the lymphoid organs and inflamed corneal tissues, MDSCs were phenotypically characterized as CD11bGr1 cells. Sorted CD11bGr1 cells, but not CD11bGr1 cells, suppressed the proliferation and cytokine production by stimulated CD4 T cells. In vitro-generated MDSCs inhibited the activity of stimulated CD4 T cells in a predominantly contact-dependent manner. An adoptive transfer of in vitro-generated MDSCs before or after ocular HSV1 infection controlled herpetic stromal keratitis lesions. The transferred MDSCs were primarily recovered from the lymphoid organs of recipients. Surprisingly, MDSCs recipients expanded their endogenous Foxp3 regulatory T cells (Tregs). We further demonstrated the MDSCs mediated stabilization of Foxp3 expression in already differentiated Tregs and their ability to cause an efficient de novo conversion of Foxp3 Tregs from stimulated Foxp3CD4 T cells. These effects occurred independent of TGF-β signaling. Therefore, the therapeutic potential of MDSCs could be harnessed as a multipronged strategy to confer an infectious tolerance to the host by activating endogenous regulatory mechanisms.
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http://dx.doi.org/10.4049/jimmunol.1900142DOI Listing
September 2019
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