Immunomodulation by filarial nematodes

Abstract

In order to chronically infect their hosts, filarial nematodes have generated a range of strategies to evade and down-modulate the host's immune system. The recent concept of suppression of immune responses by regulatory T cells has in part benefited from examinations in human and murine filariasis. Its further development in basic immunology animal models has in turn helped to better understand down-regulatory immune mechanisms in filariasis. Thus, filarial nematodes orchestrate down-regulation by inducing regulatory T cells and alternatively activated macrophages, which are able to suppress both Th1 and Th2 responses. Regulatory T cells can also induce the secretion of IgG4 from B cells as another arm of modulation. Dendritic cells are down-regulated upon first encounter with infective L3 larvae. Failure to respond to down-regulatory induction is based on genetic traits in hosts and leads to reduced parasite loads, albeit at the expense of pathology and disease. Since down-regulation in chronically and heavily infected hosts extends to third-party antigens, it is essential to analyse the impact of filarial infection for vaccination, allergy and important coinfections such as malaria, in order to foresee and avert potentially disastrous consequences of filariasis control programmes.

Habitat fragmentation and haemoparasites in the common fruit bat,Artibeus jamaicensis(Phyllostomidae) in a tropical lowland forest in Panamá

“…This could be explained by the suppressive interaction of the immune responses versus trypanosomes and Litomosoides, and in the case of Litomosoides may be even through direct modulation of the host's immune system (Hoffmann et al 2001 ;Hoerauf et al 2005).…”

Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi

“…One possibility is that IVM disrupts filarial processes that result in the modulation of the host immune system. The immunomodulatory ability of filarial nematodes generates a host phenotype characterized by suppression of both Th1 and Th2 responses, impaired proliferation of T cells, increased production of the regulatory cytokine IL-10, and higher levels of IgG4 (17). However, the molecular mechanisms that enable parasite evasion of host immune responses are incompletely understood.…”

CCL17 Controls Mast Cells for the Defense against Filarial Larval Entry

“…In the murine model of filariasis with Litomosoides sigmodontis infection, it is possible to follow the infection route from larval entry to full establishment. In this model, it has been shown that the extent of susceptibility is determined during the first days, with only a proportion of infectious L. sigmodontis stage 3 (L3) surviving and developing into adults (8). The worm load, which is maximal by day 10, stays constant for the subsequent 20 d (8).…”

“…In this model, it has been shown that the extent of susceptibility is determined during the first days, with only a proportion of infectious L. sigmodontis stage 3 (L3) surviving and developing into adults (8). The worm load, which is maximal by day 10, stays constant for the subsequent 20 d (8). Innate mechanisms must therefore exist that allow only some of the incoming larvae to migrate and develop into adults.…”