Wuchereria bancrofti-infected individuals harbor distinct IL-10-producing regulatory B and T cell subsets which are affected by anti-filarial treatment.

Manuel Ritter,Alexander Kwarteng,Achim Hoerauf,Kenneth Pfarr,Alexander Y Debrah,Laura E Layland,Linda Batsa Debrah,Yusif Mubarik,Jubin Osei-Mensah,Edward Mitre

doi:10.1371/journal.pntd.0007436

Abstract

Despite worldwide mass drug administration, it is estimated that 68 million individuals are still infected with lymphatic filariasis with 19 million hydrocele and 17 million lymphedema reported cases. Despite the staggering number of pathology cases, the majority of LF-infected individuals do not develop clinical symptoms and present a tightly regulated immune system characterized by higher frequencies of regulatory T cells (Treg), suppressed proliferation and Th2 cytokine responses accompanied with increased secretion of IL-10, TGF-β and infection-specific IgG4. Nevertheless, the filarial-induced modulation of the host`s immune system and especially the role of regulatory immune cells like regulatory B (Breg) and Treg during an ongoing LF infection remains unknown. Thus, we analysed Breg and Treg frequencies in peripheral blood from Ghanaian uninfected endemic normals (EN), lymphedema (LE), asymptomatic patent (CFA+MF+) and latent (CFA+MF-) W. bancrofti-infected individuals as well as individuals who were previously infected with W. bancrofti (PI) but had cleared the infection due to the administration of ivermectin (IVM) and albendazole (ALB). In summary, we observed that IL-10-producing CD19+CD24highCD38dhigh Breg were specifically increased in patently infected (CFA+MF+) individuals. In addition, CD19+CD24highCD5+CD1dhigh and CD19+CD5+CD1dhighIL-10+ Breg as well as CD4+CD127-FOXP3+ Treg frequencies were significantly increased in both W. bancrofti-infected cohorts (CFA+MF+ and CFA+MF-). Interestingly, the PI cohort presented frequency levels of all studied regulatory immune cell populations comparable with the EN group. In conclusion, the results from this study show that an ongoing W. bancrofti infection induces distinct Breg and Treg populations in peripheral blood from Ghanaian volunteers. Those regulatory immune cell populations might contribute to the regulated state of the host immune system and are probably important for the survival and fertility (microfilaria release) of the helminth.

Highlights

Helminths like filarial nematodes are tropical parasitic worms and the infections that they induce are classified as neglected tropical diseases (NTDs)
In this study we investigated whether W. bancrofti-infected individuals from Ghana harbored distinct Breg and Treg populations which might be important for filarial-specific immunomodulation
This study shows that W. bancrofti induces distinct Breg populations, especially in patently infected individuals who presented significantly increased frequencies of IL-10-producing CD19+CD24highCD38dhigh Breg

Summary

Introduction

Helminths like filarial nematodes are tropical parasitic worms and the infections that they induce are classified as neglected tropical diseases (NTDs). Filarial infections are vector-borne diseases which are transmitted by blood-feeding insects that are common in tropical and subtropical countries. Lymphatic filariasis (LF) is caused by Wuchereria bancrofti and Brugia spp. and can lead to the development of hydrocele, lymphedema, lymphangitis and elephantiasis causing a major public health problem and an overall elevation in disability-adjusted life years (DALY). Before mass drug administration (MDA) commenced, approximately 120 million people were infected with LF, and 40 million people suffered from disease-related pathologies. The World Health Organization launched the Global Programme to Eliminate LF (GPELF) and MDA measures have cured or prevented 96 million new cases of LF over the last 13 years. It is estimated that 68 million people are still infected and there are 19 million hydrocele and 17 million lymphedema cases [2]

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Conclusion