Immune dysregulation and inflammation causing hypopigmentation in post kala-azar dermal leishmaniasis: partners in crime?

Trends Parasitol. 2023 Oct;39(10):822-836. doi: 10.1016/j.pt.2023.07.005. Epub 2023 Aug 15.

Abstract

Post kala-azar dermal leishmaniasis (PKDL), a heterogeneous dermal sequela of visceral leishmaniasis (VL), is challenging in terms of its etiopathogenesis. Hypopigmentation is a consistent clinical feature in PKDL, but mechanisms contributing to the loss of melanocytes remains poorly defined. Like other hypopigmentary dermatoses - for example, vitiligo, psoriasis, and leprosy - the destruction of melanocytes is likely a multifactorial phenomenon, key players being immune dysregulation and inflammation. This review focuses on immunological mechanisms responsible for the 'murder' of melanocytes, prime suspects at the lesional sites being CD8+ T cells and keratinocytes and their criminal tools being proinflammatory cytokines, for example, IFN-γ, IL-6, and TNF-α. Collectively, these may cause decreased secretion of melanocyte growth factors, loss/attenuation of cell adhesion molecules and inflammasome activation, culminating in melanocyte death.

Keywords: CD8(+) T cells; cytokines; inflammasome; keratinocytes; melanocyte death; post kala-azar dermal leishmaniasis (PKDL).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Crime
  • Humans
  • Hypopigmentation*
  • Inflammation
  • Leishmaniasis, Visceral* / complications