Search

Approximately 51 million individuals suffer from lymphatic filariasis (LF) caused mainly by the filarial worm Wuchereria bancrofti. Mass drug administration (MDA) programs led to a significant reduction in the number of infected individuals, but the consequences of the treatment and clearance of infection in regard to host immunity remain uncertain. Thus, this study investigates the composition of myeloid-derived suppressor cells (MDSCs), macrophage subsets and innate lymphoid cells (ILCs), in patent (circulating filarial antigen (CFA)+ microfilariae (MF)+) and latent (CFA+MF−) W. bancrofti-infected individuals, previously W. bancrofti-infected (PI) individuals cured of the infection due to MDA, uninfected controls (endemic normal (EN)) and individuals who suffer from lymphoedema (LE) from the Western Region of Ghana. Frequencies of ILC2 were significantly reduced in W. bancrofti-infected individuals, while the frequencies of MDSCs, M2 macrophages, ILC1 and ILC3 were comparable between the cohorts. Importantly, clearance of infection due to MDA restored the ILC2 frequencies, suggesting that ILC2 subsets might migrate to the site of infection within the lymphatic tissue. In general, the immune cell composition in individuals who cured the infection were comparable to the uninfected individuals, showing that filarial-driven changes of the immune responses require an active infection and are not maintained upon the clearance of the infection. [ABSTRACT FROM AUTHOR]

Worldwide, more than 200 million people are infected with filariae which can cause severe symptoms leading to reduced quality of life and contribute to disability-adjusted life years (DALYs). In particular, lymphatic filariasis (LF) caused by Wuchereria bancrofti can lead to lymphedema (LE) and consequently presents a serious health problem. To understand why only a fraction of the infected individuals develop pathology, it is essential to understand how filariae regulate host immunity. The central role of T cells for immunity against filariae has been shown in several studies. However, there is little knowledge about T cell exhaustion, which causes T cell dysfunction and impaired immune responses, in this group of individuals. Recently, we showed that LE patients from Ghana harbor distinct patterns of exhausted effector and memory CD8+ T cell subsets. Based on these findings, we now characterized CD4+ T cell subsets from the same Ghanaian patient cohort by analyzing distinct markers within a 13-colour flow cytometry panel. We revealed that LE patients had increased frequencies of CD4+ T cells expressing exhaustion-associated receptors such as KLRG-1, TIM-3 and PD-1 compared to healthy endemic normal and W. bancrofti -infected individuals. Moreover, CD4+ T cells in LE patients were characterized by distinct co-expression patterns of inhibitory receptors. Collectively with the previous findings on CD8+ T cell exhaustion patterns, the data shown here demonstrates that filarial LE patients harbor distinct subsets of exhausted T cells. Thus, T cell exhaustion patterns in LE patients need attention especially in regards to susceptibility of concomitant infections and should be taken into consideration for LE management measures. [ABSTRACT FROM AUTHOR]

CD8+ T cells are crucial for the clearance of viral infections, and current research begins to highlight their importance in parasitic diseases too. In-depth research about characteristics of CD8+ T-cell subsets and exhaustion remains uncertain, especially during filariasis, a chronic helminth infection. Lymphatic filariasis, elicited by Wuchereria bancrofti , remains a serious health problem in endemic areas in Ghana, especially in those suffering from morbidity due to lymphedema (LE). In this observational study, the characteristics and profiles of CD8+ T cells were compared between asymptomatic Wuchereria bancrofti -infected individuals, uninfected endemic normals, and those with LE (grades 2–6). Focusing on exhausted memory (CD8+exmem: CD8+ T-betdimEomeshi) and effector (CD8+exeff: CD8+T-bethiEomesdim) CD8+ T-cell subsets, advanced flow cytometry revealed that LE individuals presented reduced frequencies of IFN-γ+CD8+exmem T cells expressing Tim-3 or LAG-3 which negatively correlated to the presence of LE. Moreover, the LE cohort further showed significantly higher frequencies of IL-10+CD8+exeff T cells expressing either Tim-3, LAG-3, CD39, KLRG-1, or PD-1, all associated markers of exhaustion, and that these frequencies positively correlated with the presence of LE. In summary, this study shows that distinct exhausted CD8+ T-cell subsets are prominent in individuals suffering from LE, suggesting that enhanced inflammation and constant immune activation might drive exhaustion of CD8+ T cells. Since T-cell exhaustion is known to be associated with insufficient control of persisting antigen, the data presented here reveals that these CD8+ T-cell exhaustion patterns in filarial LE should be taken into consideration for prevention and control management of LE. [ABSTRACT FROM AUTHOR]

Worldwide, more than 200 million people are infected with filariae which can cause severe symptoms leading to reduced quality of life and contribute to disability-adjusted life years (DALYs). In particular, lymphatic filariasis (LF) caused by Wuchereria bancrofti can lead to lymphedema (LE) and consequently presents a serious health problem. To understand why only a fraction of the infected individuals develop pathology, it is essential to understand how filariae regulate host immunity. The central role of T cells for immunity against filariae has been shown in several studies. However, there is little knowledge about T cell exhaustion, which causes T cell dysfunction and impaired immune responses, in this group of individuals. Recently, we showed that LE patients from Ghana harbor distinct patterns of exhausted effector and memory CD8 + T cell subsets. Based on these findings, we now characterized CD4 + T cell subsets from the same Ghanaian patient cohort by analyzing distinct markers within a 13-colour flow cytometry panel. We revealed that LE patients had increased frequencies of CD4 + T cells expressing exhaustion-associated receptors such as KLRG-1, TIM-3 and PD-1 compared to healthy endemic normal and W. bancrofti -infected individuals. Moreover, CD4 + T cells in LE patients were characterized by distinct co-expression patterns of inhibitory receptors. Collectively with the previous findings on CD8 + T cell exhaustion patterns, the data shown here demonstrates that filarial LE patients harbor distinct subsets of exhausted T cells. Thus, T cell exhaustion patterns in LE patients need attention especially in regards to susceptibility of concomitant infections and should be taken into consideration for LE management measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Horn, Ritter, Arndts, Borrero-Wolff, Wiszniewsky, Debrah, Debrah, Osei-Mensah, Chachage, Hoerauf, Kroidl and Layland.)