TLR Specific Immune Responses against Helminth Infections

Abstract

Despite marked improvement in the quality of lives across the globe, more than 2 million individuals in socioeconomically disadvantaged environments remain infected by helminth (worm) parasites. Owing to the longevity of the worms and paucity of immunologic controls, these parasites survive for long periods within the bloodstream, lymphatics, and gastrointestinal tract resulting in pathologic conditions such as anemia, cirrhosis, and lymphatic filariasis. Despite infection, an asymptomatic state may be maintained by the host immunoregulatory environment, which involves multiple levels of regulatory cells and cytokines; a breakdown of this regulation is observed in pathological disease. The role of TLR expression and function in relation to intracellular parasites has been documented but limited studies are available for multicellular helminth parasites. In this review, we discuss the unique and shared host effector mechanisms elicited by systemic helminth parasites and their derived products, including the role of TLRs and sphingolipids. Understanding and exploiting the interactions between these parasites and the host regulatory network are likely to highlight new strategies to control both infectious and immunological diseases.

In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases

“…The role for antibody-dependent cell-mediated cytotoxicity 46 , 66 , 67 and the TLR4 pathway in immunity to onchocerciasis has also been documented 31 . The potential role of TLR in mediating interactions between helminth parasites and the host immune system has been described 68 . Many filarial parasites (including O. volvulus ) indeed harbour a Wolbachia endosymbiont which can interact with the innate immune system through TLR2 and TLR4 69 .…”

Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases

“…The vital function of antibody-dependent cell-mediated cytotoxicity (ADCC) [ 50 , 81 , 82 ] has also been reported and research on the candidates planned for clinical trials, Ov-RAL-2 and Ov103, reported that ADCC is a crucial mechanism for a successful prophylactic vaccine against this infection [ 83 ]. The importance of TLRs in mediating interactions between helminthic parasites and the human host immune system has also been described [ 84 ] and the TLR4 pathway has been implicated in host immunity to onchocerciasis [ 38 ]. The endosymbiont Wolbachia, present in many filarial parasites (including O. volvulus ) possesses a major surface protein which interacts with the innate immune system through TLR2 and TLR4 leading to an inflammatory response characterized by proinflammatory cytokine expression in murine dendritic cells and macrophages [ 85 ].…”

A review on the interactions between dendritic cells, filarial parasite and parasite‐derived molecules in regulating the host immune responses

“…The interaction between TLRs and filarial nematode has gained special attention because these complex interactions are important for determining the immunological outcome of the disease 18 . During acute phase of filarial infection, TLR‐mediated pro‐inflammatory activation of DCs promotes Th1‐type inflammatory responses 45 …”

“…Studies have revealed that the host immune cells are mostly activated by interacting with the Toll‐like receptors (TLRs) present on the surfaces of the APCs 17 . Since the last few decades, the therapeutic potentials of these TLRs are widely accepted in case of various parasitic infections 18 . Recently, a parasite‐derived molecule known as filarial sheath antigen (FSAg) has been reported to interact with the TLR4 on host DCs 14‐16,19 …”