TLRs, Treg, and B Cells, an Interplay of Regulation during Helminth Infection

Abstract

Commonly described as masters of regulation parasitic helminth infections provide a fascinating insight into the complexity of our immune system. As with many other pathogens helminths have developed complex evasion strategies and the immune response of the host has to find a balance between eliciting severe damage to eliminate the parasite or limiting damage and thereby accepting the infection. Nevertheless, one should not forget that these infections still pose a serious public health problem and can elicit severe disfigurement or death in the individual. An interesting spin-off of helminth manipulation on host responses is the apparent prevention of autoimmune diseases or allergy although the actual mechanisms remain unclear. It is well known that Toll-like-receptors (TLR) and non-TLR PRRs play a critical role in initiating innate immune responses which in turn create appropriate adaptive immune reactions. Helminths comprise of a multitude of (glyco)-proteins and (glyco)-lipids and some have been shown to trigger TLR, or alter TLR-mediated responses. Such reactions of course alter adaptive immunity as well. This review will address the consequences of TLR-triggering by helminth antigens and the downstream effect on B cell and regulatory T cell (Treg) actions.

Patency of Litomosoides sigmodontis infection depends on Toll‐like receptor 4 whereas Toll‐like receptor 2 signalling influences filarial‐specific CD4+ T‐cell responses

“…It is well accepted that Toll‐like‐receptors (TLR) and other pathogen recognition receptors play a critical role in initiating innate immune responses, which in turn create appropriate adaptive immune reactions . Helminths comprise of a multitude of (glyco)‐proteins and (glyco)‐lipids and components have been shown to trigger pathogen recognition receptors or even alter TLR‐mediated responses . To fully understand filarial infections, one must also take into account the role of Wolbachia , an endosymbiotic third partner, which is essential for worm fecundity and survival .…”

Inhibition of cytokine response to TLR stimulation and alleviation of collagen‐induced arthritis in mice by Schistosoma japonicum peptide SJMHE1

“…As a result, the potential for exploiting worm‐based immunomodulation to treat inflammatory conditions has received increasing interest 19. However, most helminth antigens reportedly contain a large mixture of proteins, glycol‐proteins, and glycol‐lipids or whole protein 7, 8, 32. These mixture molecules or whole proteins may cross‐link adjacent IgE on mast cells and basophils, or activate pathogenic B and T cells, thereby exacerbating the allergy or autoimmune response 33, 34.…”

“…The suppression mechanism is associated with immunomodulation induced by the interactions of schistosome‐derived antigens with immune cells of hosts 2. Some phospholipids or glycoproteins from helminthes ligate toll‐like receptors (TLRs), thereby inducing an anti‐inflammatory phenotype 7, 8. A phosphorylcholine‐containing glycoprotein called ES‐62, which comes from the nematode Acanthocheilonema viteae , modulates antigen‐presenting cell activation by a variety of TLR ligands 9.…”

Regulation of the host immune system by helminth parasites

“…A key association has emerged between helminth infection and expansion of regulatory cell populations, most importantly the Treg cell subset 17, 18, 33. In human subjects Treg cells expressing the transcription factor forkhead box protein 3 (Foxp3) are more numerous and more active in helminth-infected subjects but decrease after anthelmintic chemotherapy 19, 34, 35.…”