Pathogen Strategies to Evade Innate Immune Response: A Signaling Point of View

Abstract

An effective host defense against pathogens requires appropriate recognition of the invading microorganism by immune cells, conducing to an inflammatory process that involves recruitment of leukocytes to the site of infection, activation of antimicrobial effector mechanisms and induction of an adaptive immune response that ultimately will promote the clearance of infection. All these events require the coordination of multiple signaling pathways, initially triggered by the contact of the pathogen with innate immune cells. The “signal alarm” is normally triggered by ligation of microorganism, or microorganism’s components, to pattern-recognition receptors, causing their phosphorylation and recruitment of adapter molecules, which in turn will activate second messengers within the cytosol of the cells, allowing the transduction of the signal. The second messengers are often protein kinases that in a cascade process ultimately activate the transcription factors responsible for the expression of effector molecules like, cytokines, chemokines and reactive oxygen species, crucial elements to mount an adequate immune response. The activity of such critical intracellular signaling pathways is a process extremely well controlled by a balance of positive and negative regulation, being the activation of a given protein kinase normally counterbalanced by the activation of its opposing phosphatase. However, as part of their pathogenic strategies, several microorganisms exploit host cell signaling mechanisms by distorting this balance between positive and negative signals. They hijack crucial immunecell signaling pathways, subverting the immunogenic abilities of these cells and evading this way the host immune response. In the last few years a great effort has gone into understanding the molecular mechanisms behind this subversion, and various signaling cascades were identified as main targets of pathogens and virulence factors. Among these targets, assume particular importance the transcription factor nuclear factor-κB (NF-κB), a cornerstone of innate immunity and inflammatory responses, as well as the mitogen activated protein kinases (MAPKs), signaling cascades implicated in the regulation of crucial aspects of immunity. Overall in this chapter, we will provide an overview of the current understanding of how pathogens interact with host cells and how these microorganisms exploit host immune response in a signaling point of view.