Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses

Abstract

SUMMARY The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications.

Behavioral fever in ectothermic vertebrates

“…the Toll-like receptors (TLR), which recognize conserved structures of microorganisms or signatures of tissue lesion (O'Neill et al, 2013). These PRR are expressed by innate immune cells including macrophages, dendritic cells and neutrophils and upon activation, trigger proinflammatory and antimicrobial reactions (Mogensen, 2009). Notably, their activation induces the release of pyrogenic cytokines called endogenous pyrogens such as interleukin (IL) 1b, IL6, tumor necrosis factor a (TNFa), and interferons (IFN) (Dinarello, 1999;Netea et al, 2000).…”

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

“…TLRs 1, 2, 4, 6, and 10 are involved in lipid recognition, TLRs 5 and 11 recognize proteins, and TLRs 3, 7, 8, and 9 detect nucleic acids. 56,57 Upon ligation, TLRs form homo-and heterodimers. TLR-mediated signals are transduced via 2 major signaling pathways dependent or independent of the Myeloid differentiation primary response protein (88) (MyD88).…”

Innate immunity in diabetes and diabetic nephropathy

“…These mechanisms include the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). In addition to sensing microorganism byproducts, the immune system has evolved to detect endogenous danger signals through the sensing of danger-associated molecular patterns (DAMPs) 6 . DAMPs are derived from damaged or dying cells, and include small molecules (ATP and DNA), particles (uric acid crystals and exogenous noxious factors such as asbestos) and environmental insults such as UV irradiation 7 .…”