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.
Part of the book: Toll-like Receptors
The gut microbiome consists of bacteria, protozoans, viruses, and archaea collectively called as gut microbiota. Gut microbiome (GM) modulates a variety of physiological responses ranging from immune and inflammatory responses, neuronal signalling, gut barrier integrity and mobility, synthesis of vitamins, steroid hormones, neurotransmitters to metabolism of branched-chain aromatic amino acids, bile salts, and drugs. Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder that is featured by imbalance in blood glucose level, altered lipid profile, and their deleterious consequences. GM dysbiosis a major factor behind the incidence and progression of insulin resistance and is responsible for altering of intestinal barrier functions, host metabolic, and signaling pathways. The GM of type 2 diabetes (T2DM) patients is characterized by reduced levels of Firmicutes and Clostridia and an increased ratio of Bacteroidetes:Firmicutes. Endotoxemia stimulates a low-grade inflammatory response, which is known to trigger T2DM. Xenobiotics including dietary components, antibiotics, and nonsteroidal anti-inflammatory drugs strongly affect the gut microbial composition and can promote dysbiosis. However, the exact mechanisms behind the dynamics of gut microbes and their impact on host metabolism are yet to be deciphered. Interventions that can restore equilibrium in the GM have beneficial effects and can improve glycemic control.
Part of the book: Parasitology and Microbiology Research