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Toll-like receptors and damage-associated molecular patterns in the pathogenesis of heart transplant rejection

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Abstract

Significant strides have been made in our understanding of the immune system and its role in cardiac transplant rejection. Despite the growing knowledge of immune responses, the mortality rate following cardiac transplantation remains grim. Related to procedural and pathological complications, toll-like receptor (TLR) and damage-associated molecular pattern (DAMP) signaling is the most direct and earliest interface between tissue integration and the innate immune response. This in turn can activate an adaptive immune response that further damages myocardial tissue. Furthermore, relevant literature on the status of DAMPs in the context of heart-transplantation remains limited, warranting further attention in clinical and translational research. This review aims to critically appraise the perspectives, advances, and challenges on DAMP-mediated innate immune response in the immune-mediated rejection of cardiac transplantation. Detailed analysis of the influence of TLR and DAMP signaling in mounting the immune response against the transplanted heart holds promise for improving outcomes through early detection and prevention of varied forms of organ rejection.

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Acknowledgements

The figure was created using BioRender.com

Funding

The research work of DK Agrawal is supported by NIH-NHLBI Grants R01HL147662 and R01HL144125. The content of this original review article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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  1. Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766-1854, USA

    Alice Kesler, Devendra K. Agrawal & Finosh G. Thankam

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  1. Alice Kesler
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  2. Devendra K. Agrawal
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  3. Finosh G. Thankam
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Contributions

Conception and design: FGT; Literature search, collection of the scientific information, analysis, and interpretation of the data: AK, DKA, FGT; Drafting of the article: AK, FGT; Critical revision and editing of the article for important intellectual content: FGT, DKA; Final approval of the submitted article: AK, DKA, FGT.

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Correspondence to Finosh G. Thankam.

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Kesler, A., Agrawal, D.K. & Thankam, F.G. Toll-like receptors and damage-associated molecular patterns in the pathogenesis of heart transplant rejection. Mol Cell Biochem 477, 2841–2850 (2022). https://doi.org/10.1007/s11010-022-04491-4

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