TLR Signaling on Protozoan and Helminthic Parasite Infection

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 Toll-interleukin1 (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.

Vaccination against the Protozoan Parasite Histomonas meleagridis Primes the Activation of Toll-like Receptors in Turkeys and Chickens Determined by a Set of Newly Developed Multiplex RT-qPCRs

“…However, in both species the local TLR expression was clearly increased, whereas the systemic immune response had a minor alteration. It is well known that in the acute stage of local inflammation different TLRs related with inflammation—such as TLR2 and 4 —are expressed [ 32 ]. This was shown to be caused by host cells with direct contact to the pathogens as described earlier [ 33 ].…”

Immunopathogenicity of Acanthamoeba spp. in the Brain and Lungs

“…Relatively few studies have looked at TLR response induction in parasite infections. Parasites can both activate and inhibit the signal across TLRs [ 68 ], but the role of these mechanisms in the parasite–host interaction requires further research. Massilamany et al [ 69 ] characterized the inflammatory cells in the brains and spinal cords of Acanthamoeba castellanii infected mice.…”

Modulation of the Innate Immune Response by Targeting Toll-like Receptors: A Perspective on Their Agonists and Antagonists

“…133,134 To date, no vaccine has been approved for the prevention of these major problems, thus indicating the need for a better understanding of the pathogenesis of such diseases and even more of the mechanism by which the host immune system recognizes and faces the parasites. 135 Nowadays, research efforts led to the identifications of the PAMPs recognized by host immune system and the pathways involved in the inflammation and resolution processes (reviewed by Babu et al). 136 Unfortunately, the application of TLR agonists/antagonists led to few or unsatisfactory results in parasites clearance.…”

“…Therefore, considering the involvement of multiple TLRs in the recognition of plasmodial components, it is conceivable that the pan-TLR inhibitors developed by Pollock et al could represent an alternative approach for the management of malaria . Other parasitic diseases, such as trypanosomiasis, leishmaniasis, and schistosomiasis, represent a huge socioeconomic burden and leading causes of death, in endemic areas. , To date, no vaccine has been approved for the prevention of these major problems, thus indicating the need for a better understanding of the pathogenesis of such diseases and even more of the mechanism by which the host immune system recognizes and faces the parasites . Nowadays, research efforts led to the identifications of the PAMPs recognized by host immune system and the pathways involved in the inflammation and resolution processes (reviewed by Babu et al.)…”