Toll like receptors (TLRs) are evolutionarily conserved receptors belonging to the family of pattern recognition receptors (PRRs), which are important mediators of inflammatory pathways within the gut. They play a major role in mediating immune responses towards a wide variety of pathogen-derived ligands and link adaptive immunity to innate immunity. TLRs are directly involved in the activation of innate or adaptive immune responses for the elimination of infectious pathogens and cancer debris. TLRs are one of the best characterized PRR families, which function to recognize self and non-self antigens, detect various pathogens, bridge innate and adaptive immunity, and regulate cytokine production, regulate the proliferation and survival of the host cell. Different TLRs function to recruit different immune cells and varied mechanisms to dominate foreign pathogens, endogenous molecules, or malignancies. The external ligands of pathogen-associated molecular patterns (PAMPs) and internal ligands of damage-associated molecular patterns (DAMPs) activate the TLRs and the two main downstream signaling pathways causing the cascade of changes within the host. Once the cascading adaptor molecules are activated, they result in the activation of transcription factors, like nuclear factor-kB (NFkB), interferons, mitogen-activated protein (MAP) kinases, and response factors (IRFs), all of which play a role in the inflammatory response against pathogen or irritants. Because of their inherent nature of modulating inflammation, TLRs may serve as a double-edged sword with both positive and negative roles in human health and disease. The innate and adaptive immune cells as well as non-immune system cells cooperate with TLRs and act as an organized harmonic orchestra. Interleukins, cytokines, and chemokines (including pro-inflammatory ones), cell proliferation, apoptosis, repair, and reconstruction mechanisms are supported by TLRs. Hence, they can be recognized as pivotal molecules in various human auto-immune, pathogenic infectious diseases as well as various malignancies. Numerous studies in different populations across the continents have reported on the significant roles of TLR gene polymorphisms in modulating the risk of various diseases, especially cancer, autoimmune diseases, and infections.

The aim of this Special Issue is invite original and review articles discussing all known TLR signaling pathways, the mechanisms by which TLRs regulate inflammatory processes, various cells, and molecules which contribute to the TLR functioning within the cell, the relation of TLR signaling with human health, infectious diseases, autoimmune diseases, cancer, the role played by various TLR SNPs in susceptibility to human diseases and identification of TLR as the novel candidates for therapeutic strategies.

Potential topics include but are not limited to the following:

• Structure and Molecular biology of TLRs
• TLR signaling pathways
• TLRs and mechanisms of immune modulation
• TLRs and genetic variations, mutations, and polymorphisms
• TLRs in health and disease
• TLRs in infectious diseases
• TLRs in autoimmune diseases
• TLRs in tumorigenesis
• TLRs as therapeutic strategies
• TLRs as disease biomarkers
• TLR SNPs in human diseases
• TLR SNPs in autoimmune diseases
• TLR SNPs in cancers