Dataset Information

Stage-Dependent Increase of Systemic Immune Activation and CCR5⁺CD4⁺ T Cells in Filarial Driven Lymphedema in Ghana and Tanzania.

ABSTRACT: Chronic lymphedema caused by infection of Wuchereria bancrofti is a disfiguring disease that leads to physical disability, stigmatization, and reduced quality of life. The edematous changes occur mainly on the lower extremities and can progress over time due to secondary bacterial infections. In this study, we characterized participants with filarial lymphedema from Ghana and Tanzania as having low (stage 1-2), intermediate (stage 3-4), or advanced (stage 5-7) lymphedema to determine CD4⁺ T cell activation patterns and markers associated with immune cell exhaustion. A flow cytometry-based analysis of peripheral whole blood revealed different T cell phenotypes within participants with different stages of filarial lymphedema. In detail, increased frequencies of CD4⁺HLA-DR⁺CD38⁺ T cells were associated with higher stages of filarial lymphedema in patients from Ghana and Tanzania. In addition, significantly increased frequencies of CCR5⁺CD4⁺ T cells were seen in Ghanaian participants with advanced LE stages, which was not observed in the Tanzanian cohort. The frequencies of CD8⁺PD-1⁺ T cells were augmented in individuals with higher stage lymphedema in both countries. These findings show distinct activation and exhaustion patterns in lymphedema patients but reveal that immunological findings differ between West and East African countries.

SUBMITTER: Rahamani AA

PROVIDER: S-EPMC10301430 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Stage-Dependent Increase of Systemic Immune Activation and CCR5+CD4+ T Cells in Filarial Driven Lymphedema in Ghana and Tanzania.

Rahamani Abu Abudu AA Horn Sacha S Ritter Manuel M Feichtner Anja A Osei-Mensah Jubin J Serwaa Opoku Vera V Batsa Debrah Linda L Marandu Thomas F TF Haule Antelmo A Mhidze Jacklina J Ngenya Abdallah A Demetrius Max M Klarmann-Schulz Ute U Hoelscher Michael M Geldmacher Christof C Hoerauf Achim A Kalinga Akili A Debrah Alexander Y AY Kroidl Inge I

Pathogens (Basel, Switzerland) 20230607 6

Chronic lymphedema caused by infection of Wuchereria bancrofti is a disfiguring disease that leads to physical disability, stigmatization, and reduced quality of life. The edematous changes occur mainly on the lower extremities and can progress over time due to secondary bacterial infections. In this study, we characterized participants with filarial lymphedema from Ghana and Tanzania as having low (stage 1-2), intermediate (stage 3-4), or advanced (stage 5-7) lymphedema to determine CD4< ...[more]

PMID: 37375499

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Project description:BackgroundLymphedema is an intractable disease that can be caused by injury to lymphatic vessels, such as by surgical treatments for cancer. It can lead to impaired joint mobility in the extremities and reduced quality of life. Chronic inflammation due to infiltration of various immune cells in an area of lymphedema is thought to lead to local fibrosis, but the molecular pathogenesis of lymphedema remains unclear. Development of effective therapies requires elucidation of the immunological mechanisms involved in the progression of lymphedema. The complement system is part of the innate immune system which has a central role in the elimination of invading microbes and acts as a scavenger of altered host cells, such as apoptotic and necrotic cells and cellular debris. Complement-targeted therapies have recently been clinically applied to various diseases caused by complement overactivation. In this context, we aimed to determine whether complement activation is involved in the development of lymphedema.ResultsOur mouse tail lymphedema models showed increased expression of C3, and that the classical or lectin pathway was locally activated. Complement activation was suggested to be involved in the progression of lymphedema. In comparison of the C3 knockout (KO) mouse lymphedema model and wild-type mice, there was no difference in the degree of edema at three weeks postoperatively, but the C3 KO mice had a significant increase of TUNEL+ necrotic cells and CD4+ T cells. Infiltration of macrophages and granulocytes was not significantly elevated in C3 KO or C5 KO mice compared with in wild-type mice. Impaired opsonization and decreased migration of macrophages and granulocytes due to C3 deficiency should therefore induce the accumulation of dead cells and may lead to increased infiltration of CD4+ T cells.ConclusionsVigilance for exacerbation of lymphedema is necessary when surgical treatments have the potential to injure lymphatic vessels in patients undergoing complement-targeted therapies or with complement deficiency. Future studies should aim to elucidate the molecular mechanism of CD4+ T cell infiltration by accumulated dead cells.

Dataset Information

Stage-Dependent Increase of Systemic Immune Activation and CCR5⁺CD4⁺ T Cells in Filarial Driven Lymphedema in Ghana and Tanzania.

Publications

Stage-Dependent Increase of Systemic Immune Activation and CCR5<sup>+</sup>CD4<sup>+</sup> T Cells in Filarial Driven Lymphedema in Ghana and Tanzania.

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