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

TY - JOUR

T1 - Immune dysregulation and inflammation causing hypopigmentation in post kala-azar dermal leishmaniasis

T2 - partners in crime?

AU - Sengupta, Ritika

AU - Roy, Madhurima

AU - Dey, Nidhi S

AU - Kaye, Paul M

AU - Chatterjee, Mitali

N1 - Funding Information: The work received financial assistance to M.C. as a J.C. Bose Fellowship, Govt. of India ( JCB/2019/000043 ); R.S. and M.R. are recipients of Senior Research Fellowship from Indian Council of Medical Research, ICMR, Govt. of India and University Grants Commission, respectively. Funding Information: The work received financial assistance to M.C. as a J.C. Bose Fellowship, Govt. of India (JCB/2019/000043); R.S. and M.R. are recipients of Senior Research Fellowship from Indian Council of Medical Research, ICMR, Govt. of India and University Grants Commission, respectively. The authors declare no competing interests. Publisher Copyright: © 2023

PY - 2023/9/13

Y1 - 2023/9/13

N2 - 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.

AB - 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.

KW - Humans

KW - Leishmaniasis, Visceral/complications

KW - CD8-Positive T-Lymphocytes

KW - Hypopigmentation

KW - Crime

KW - Inflammation

UR - http://www.scopus.com/inward/record.url?scp=85168358825&partnerID=8YFLogxK

U2 - 10.1016/j.pt.2023.07.005

DO - 10.1016/j.pt.2023.07.005

M3 - Review article

C2 - 37586987

AN - SCOPUS:85168358825

SN - 1471-4922

VL - 39

SP - 822

EP - 836

JO - Trends in parasitology

JF - Trends in parasitology

IS - 10

ER -