Author(s):
Neves, Bruno Miguel 
; Lopes, Maria Celeste ; Cruz, Maria Teresa
Date: 2012
Persistent ID: http://hdl.handle.net/10773/10532
Origin: RIA - Repositório Institucional da Universidade de Aveiro
Subject(s): Infection; Innate Immune Response; Pathogen evasion; Signaling cacades; Protein kinases
Description
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.
