TLR Signaling on Protozoan and Helminthic Parasite Infection

*Chandrani Fouzder, Alpana Mukhuty, Snehasis Das and Dipanjan Chattopadhyay*

#### **Abstract**

Toll-like receptors (TLRs), a major component of innate immune system, are expressed as membrane or cytosolic receptors on neutrophils, monocytes, macrophages, dendritic cells (DCs), B lymphocytes, Th1, Th2, and regulatory T lymphocytes. It recognizes pathogen-associated molecular patterns (PAMPs) and Tollinterleukin1 (IL-1) receptor (TIR) of various invading pathogens. Downstream signaling of TLRs activates NF-κB, which acts as a transcription factor of pro-inflammatory cytokines, chemokines, and costimulatory molecules. A balance between pro- and anti-inflammatory cytokine protects host body from infectious agents and also induces the healing process. Some of parasitic infections by protozoans and helminths such as Malaria, Leishmaniasis, Trypanosomiasis, Toxoplasmosis, Amoebiasis, Filariasis, Schistosomiasis, Ascariasis, Taeniasis, and Fasciolosis are the leading cause of death and economic loss in both developing and developed nations. Frequent exposure to parasites, immigration, refugee resettlement, increasing immunodeficiency, climate change, drug resistance, lack of vaccination, etc. are the major cause of emerging and re-emerging of the above-stated diseases. However, TLR activation by parasites could stimulate antigen presenting cells and ultimately clear the pathogens by phagocytosis. So, a better understanding of host-parasite interaction in relation to TLR signaling pathway will improve the controlling method of these pathogens in immunotherapy.

**Keywords:** Toll-like receptors, pathogen-associated molecular patterns, protozoan parasite, helminth infection

#### **1. Introduction**

Increasing cases of parasitic infections (due to protozoans and helminths) and high rate of mortality are the greatest problem of today's world. Some of these diseases such as Malaria, Filariasis, Trypanosomiasis, Leishmaniasis, Toxoplasmosis, Amoebiasis, Ascariasis, Schistosomiasis, and Taeniasis affect over half a billion people worldwide and cause economic loss in both developing and developed countries [1]. Overpopulations, migration of people into large urban areas, and unhygienic environment are the main reasons for making these diseases epidemic [2]. However, the tragedy is that only 5% of total health expenditure was given for research work on parasitic diseases [3]. Currently, there is no effective vaccine available for these major problems. So, a better understanding of pathogenesis during infection, resistance mechanism of pathogens, host protective immune response initiation, and progression is needed for developing effective vaccines or therapeutic interventions [4].

Among the two types of vertebrate immune system, innate immunity provides the first line of defense against parasites. Previous studies stated innate immunity as nonspecific response, and it induces the acquired immunity (slower and specific response) by providing pathogens to T and B cells [5]. However, recent evidence proved that innate immune system also had a great degree of specificity and can provide host defense against invading parasites. This is because of the presence of five classes of pattern recognition receptors: TLRs (Toll-like receptors), C-type lectin receptors, NOD-like receptors (nucleotide-binding oligomerization domain leucine-rich repeat-containing receptors), RIG-I (retinoic acid inducible gene I protein) helicase receptors, and cytosolic dsDNA sensors [6, 7]. Among them, TLRs form a bridge between innate and adaptive immunity and play a very important role in parasite eradication. TLRs recognize specific pathogen-associated molecular patterns (PAMPs) in pathogens and initiate opsonization, phagocytosis, proinflammatory and anti-inflammatory response, and apoptosis [7, 8].
