NF- κB Signaling in Macrophages: Dynamics, Crosstalk, and Signal Integration

Conclusions NF-κB is a master regulator of innate immune responses, and vital to many of the roles that macrophages and other innate immune cells play in orchestrating the inflammatory response to pathogens. In this review, we have outlined the many variables that influence the outcomes of NF-κB signaling, including those that are cell-, tissue-, and stimulus-specific. Over 30 years of research has illuminated the dynamics of this signaling pathway and the genes that are regulated by it, leading to many breakthroughs in how we understand NF-κB function. However, much of this information has come from studying non-hematopoietic cells or pathway components in cell-free conditions. As new technologies and techniques have been developed over the past decade, it has become feasible to study NF-κB signaling in less tractable cell models such as primary macrophages as well as in vivo. Recent studies, outlined above, have highlighted differences in signaling dynamics in these contexts which act to support the goals of the innate immune system—that is, to regulate and tailor the inflammatory response to pathogens in order to balance the destruction of invaders with the limitation of potentially harmful hyperinflammation. Macrophages are capable of integrating an impressive amount of information regarding the identity and virulence of pathogens, as well as endogenous cues present in their microenvironment, in order to modulate the immune respon...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research