The importance of T cell-derived cytokines in post-kala-azar dermal leishmaniasis

Jafarzadeh, Abdollah; Jafarzadeh, Sara; Sharifi, Iraj; Aminizadeh, Najmeh; Nozari, Parvin; Nemati, Maryam

doi:10.1016/j.cyto.2020.155321

Cited by 12 publications

(5 citation statements)

References 96 publications

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“…Similarly in human leishmaniasis, T REG cells were characterized in skin lesions of patients with CL, PKDL, and MCL caused by different New World and Old World Leishmania species, suggesting a regulatory role of these cells through IL-10 production that contributes to the parasite persistence ( 53 , 76 , 101 , 102 ).…”

Section: Persistent Parasites and Concomitant Immunitymentioning

confidence: 99%

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

Nateghi-Rostami,

Sohrabi

2024

Front. Immunol.

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Understanding the immune response to Leishmania infection and identifying biomarkers that correlate with protection are crucial for developing effective vaccines. One intriguing aspect of Leishmania infection is the persistence of parasites, even after apparent lesion healing. Various host cells, including dendritic cells, fibroblasts, and Langerhans cells, may serve as safe sites for latent infection. Memory T cells, especially tissue-resident memory T cells (TRM), play a crucial role in concomitant immunity against cutaneous Leishmania infections. These TRM cells are long-lasting and can protect against reinfection in the absence of persistent parasites. CD4+ TRM cells, in particular, have been implicated in protection against Leishmania infections. These cells are characterized by their ability to reside in the skin and rapidly respond to secondary infections by producing cytokines such as IFN-γ, which activates macrophages to kill parasites. The induction of CD4+ TRM cells has shown promise in experimental immunization, leading to protection against Leishmania challenge infections. Identifying biomarkers of protection is a critical step in vaccine development and CD4+ TRM cells hold potential as biomarkers, as their presence and functions may correlate with protection. While recent studies have shown that Leishmania-specific memory CD4+ T-cell subsets are present in individuals with a history of cutaneous leishmaniasis, further studies are needed to characterize CD4+ TRM cell populations. Overall, this review highlights the importance of memory T cells, particularly skin-resident CD4+ TRM cells, as promising targets for developing effective vaccines against leishmaniasis and as biomarkers of immune protection to assess the efficacy of candidate vaccines against human leishmaniasis.

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Section: Persistent Parasites and Concomitant Immunitymentioning

confidence: 99%

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

Nateghi-Rostami,

Sohrabi

2024

Front. Immunol.

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“…The keratinocyte‐derived chemokines play an essential role in recruiting of the neutrophils, monocytes, NK cells, TH1, TH2, Treg and TH17 cells into the inflamed/infected skin 20 . For example, CXCL1‐6 and CXCL8 can attract neutrophils; CCL2 and CCL3 can attract monocytes and macrophages; CCL2 can attract NK cells; CXCL9, CXCL10 and CXCL11 can attract TH1 cells; CCL17 and CCL22 can attract TH2, Treg cells and CCR4 + CD8 + T cells; and CCL20 can attract TH17 cells into the Leishmania ‐infected skin 3,24,25 . Further, the keratinocyte‐derived CCL27 and CCL20 recruit CCR10 and CCR6 expressing T cells to noninflamed tissue, respectively 15 .…”

Section: Leishmaniasis and Keratinocyte‐mediated Immune Responsesmentioning

confidence: 99%

“…The cutaneous leishmaniasis (CL) is caused by L major and L tropica in the Middle East and North Africa, whereas the same disease is caused by L mexicana and L braziliensis in the America 1,2 . L amazonensis causes anergic diffuse CL (DCL) whereas L donovani and L infantum cause visceral leishmaniasis (VL), which when treated may lead to PKDL in some patients 1,3 …”

Section: Introductionmentioning

confidence: 99%

Immunological role of keratinocytes in leishmaniasis

Jafarzadeh

Nair²,

Jafarzadeh

et al. 2021

Parasite Immunology

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Following inoculation of Leishmania, a protozoan parasite, into the skin of a mammal, the epidermal keratinocytes recognize the parasite and influence the local immune response that can give rise to different outcomes of leishmaniasis. The early keratinocyte‐derived cytokines and keratinocytes‐T cells interactions shape the anti‐leishmanial immune responses that contribute to the resistance or susceptibility to leishmaniasis. The keratinocyte‐derived cytokines can directly potentiate the leishmanicidal activity of monocytes and macrophages. As keratinocytes express MHC‐II and enhance the expression of costimulatory molecules, these cells act as antigen‐presenting cells (APCs) in cutaneous leishmaniasis (CL). Depending on the epidermal microenvironment, the keratinocytes induce various types of effector CD4+ T cells. Keratinocyte apoptosis and necrosis have been also implicated in ulceration in CL. Further, keratinocytes contribute to the healing of Leishmania‐related cutaneous wounds. However, keratinocyte‐derived IL‐10 may play a key role in the development of post‐kala‐azar dermal leishmaniasis (PKDL). In this review, a comprehensive discussion regarding the multiple roles played by keratinocytes during leishmaniasis was provided, while highlighting novel insights concerning the immunological and pathological roles of these cells.

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“…PKDL is characterized by a cutaneous rash on exposed body parts, such as the face, ears, and hands, and can also affect other areas of the body during progression ( 10 ). In some patients, PKDL appears without any prior episode of VL while inadequate treatment also increases the chances of PKDL development ( 11 ). While PKDL has relatively no mortality compared to VL, it carries significant socioeconomic implications and PKDL patients serve as a reservoir for parasites, thus contributing to parasite transmission and potential new VL cases ( 1 , 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Post kala-azar dermal leishmaniasis in the Indian sub-continent: challenges and strategies for elimination

et al. 2023

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Visceral leishmaniasis (VL) is a severe and often fatal form of leishmaniasis caused by Leishmania donovani in the Indian sub-continent. Post Kala-azar Dermal Leishmaniasis (PKDL) is a late cutaneous manifestation of VL, typically occurring after apparent cure of VL, but sometimes even without a prior history of VL in India. PKDL serves as a significant yet neglected reservoir of infection and plays a crucial role in the transmission of the disease, posing a serious threat to the VL elimination program in the Indian sub-continent. Therefore, the eradication of PKDL should be a priority within the current VL elimination program aimed at achieving a goal of less than 1 case per 10,000 in the population at the district or sub-district levels of VL endemic areas. To accomplish this, a comprehensive understanding of the pathogenesis of PKDL is essential, as well as developing strategies for disease management. This review provides an overview of the current status of diagnosis and treatment options for PKDL, highlighting our current knowledge of the immune responses underlying disease development and progression. Additionally, the review discusses the impact of PKDL on elimination programs and propose strategies to overcome this challenge and achieve the goal of elimination. By addressing the diagnostic and therapeutic gaps, optimizing surveillance and control measures, and implementing effective intervention strategies, it is possible to mitigate the burden of PKDL and facilitate the successful elimination of VL in the Indian sub-continent.

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The importance of T cell-derived cytokines in post-kala-azar dermal leishmaniasis

Cited by 12 publications

References 96 publications

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

Immunological role of keratinocytes in leishmaniasis

Post kala-azar dermal leishmaniasis in the Indian sub-continent: challenges and strategies for elimination

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