Thymic and Peripheral T-cell Polarization in an Experimental Model of Russell’s Viper Venom-induced Acute Kidney Injury

ABSTRACT

Venom pathology is not restricted to the direct toxic effects of venom. Immunoinflammatory alteration as the etiology of snake venom-induced acute kidney injury (SAKI) is a less trodden path toward the development of alternative therapeutic approach. In the present study, we have associated the crest of renal damage stage to the immunological alteration, as reflected in thymic and peripheral T cell polarization in the murine model of SAKI. Renal injury in mice was confirmed from significant dysuresis and adversely altered biochemical renal markers. Histopathological alterations, as revealed by marked tubular and glomerular damage, reaffirmed kidney injury. SAKI is accompanied by significant inflammatory changes as indicated by neutrophilic leucocytosis, increased neutrophil to lymphocyte ratio and plasma CRP levels. Thymic immunophenotyping revealed significantly increased CD8⁺ cytotoxic T cell, and CD25⁺ both single positive population (p = .017–0.010) and CD44⁻CD25⁺ double negative population (DN3) (p = .002) accompanied by an insignificantly reduced CD4⁺ helper T cells (p = .451). Peripheral immunophenotyping revealed similar pattern as indicated by reduced helper T cells (p = .002) associated with significantly elevated cytotoxic T cells (p = .009) and CD25⁺ subset of both helper (p = .002) and cytotoxic (p = .024) T cells. The IL-10⁺ subset of both CD25⁺ and CD25⁻ T cells were also found to be significantly elevated in the SAKI group (p ≤ 0.020) suggesting an immunosuppressive phenotype in SAKI. It can be concluded that T cells responds to venom-induced renal injury particularly through IL-10⁺ reparative phenotypes which are known for their immunosuppressive and anti-inflammatory activity.

KEYWORDS:

• Acute kidney injury
• CD8⁺ T cells
• IL-10
• peripheral CD25⁺ T cells
• snake venom
• thymic CD25⁺ T cells

Acknowledgments

We are thankful to the Directorate of Forest, Government of West Bengal, for the permission to collect the snake venom in West Bengal and to Mr. Vishal Santra, Herpetologist, for venom collection on our behalf. We are also thankful to the Centre for Research in Nanoscience and Nanotechnology (CRNN) and University of Calcutta for the infrastructural support. We are grateful to Dr. Keya Basu, Associate Professor, Department of Pathology, IPGME&R, Kolkata for her generous help during thymic histological studies and interpretations.

Disclosure Statement

The authors declare no conflict of interest.

Additional information

Funding

The work reported is supported by grants from West Bengal Department of Higher Education Science & Technology and Biotechnology (WBDHEST&BT) Sanction No: 41(Sanc.)-BT/ST/P/S&T/2G-14/2017, Dated 16.02.2018 and UGC-UPEII (Sub-Group- A2).