Abstract
Infection with filarial parasites is associated with T cell hyporesponsiveness, which is thought to be partly mediated by their ability to induce regulatory T cells (Tregs) during human infections. This study investigates the functional capacity of Tregs from different groups of filarial patients to suppress filaria-specific immune responses during human filariasis. Microfilaremic (MF), chronic pathology (CP) and uninfected endemic normal (EN) individuals were selected in an area endemic for Brugia timori in Flores island, Indonesia. PBMC were isolated, CD4CD25hi cells were magnetically depleted and in vitro cytokine production and proliferation in response to B. malayi adult worm antigen (BmA) were determined in total and Treg-depleted PBMC. In MF subjects BmA-specific T and B lymphocyte proliferation as well as IFN-gamma, IL-13 and IL-17 responses were lower compared to EN and CP groups. Depletion of Tregs restored T cell as well as B cell proliferation in MF-positives, while proliferative responses in the other groups were not enhanced. BmA-induced IL-13 production was increased after Treg removal in MF-positives only. Thus, filaria-associated Tregs were demonstrated to be functional in suppressing proliferation and possibly Th2 cytokine responses to BmA. These suppressive effects were only observed in the MF group and not in EN or CP. These findings may be important when considering strategies for filarial treatment and the targeted prevention of filaria-induced lymphedema.
Highlights
Lymphatic filariasis (LF), caused by nematodes Wuchereria bancrofti, Brugia malayi and B. timori, affects around 120 million people worldwide and 2 billion people are at risk in endemic areas [1]
Lymphatic filariasis is a neglected disease still prominent in low-resource settings and is very disabling when it progresses to chronic pathology caused by lymphedema
We have looked at the functional consequence of the presence of Tregs in filaria-specific immune responses during different stages of human lymphatic filariasis
Summary
Lymphatic filariasis (LF), caused by nematodes Wuchereria bancrofti, Brugia malayi and B. timori, affects around 120 million people worldwide and 2 billion people are at risk in endemic areas [1]. All three filarial parasites are prevalent in the archipelago and efforts are being made to control the disease in various areas (Global Programme to Eliminate Lymphatic Filariasis) [2,3]. Helminths such as filarial parasites have been shown to induce immune modulation, resulting in T cell hyporesponsiveness and failure to expel parasites [4]. With circulating microfilariae (MF) and/or filarial antigens, decreased proliferative responses and increased anti-inflammatory cytokines, such as IL-10 and TGF-b, reflect a state of immune hyporesponsiveness [6]. In patients with chronic pathology this seems to be reversed; in PBMC from these patients enhanced inflammatory Th1 and Th17 responses as well as decreased levels of mRNA for different Treg markers were observed as compared to asymptomatic infected individuals [8]
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