Does Infection-Induced Immune Activation Contribute to Dementia?

Allan Allan,Meagan Rp Meagan Rp,Lutiana Rs Lutiana Rs,Felipe D Felipe D,Jaqueline Jaqueline,Tatiana Tatiana,Jessica Jessica,João Q João Q

doi:10.14336/ad.2015.0521

Abstract

The central nervous system (CNS) is protected by a complex blood-brain barrier system; however, a broad diversity of virus, bacteria, fungi, and protozoa can gain access and cause illness. As pathogens replicate, they release molecules that can be recognized by innate immune cells. These molecules are pathogen-associated molecular patterns (PAMP) and they are identified by pattern-recognition receptors (PRR) expressed on antigen-presenting cells. Examples of PRR include toll-like receptors (TLR), receptors for advanced glycation endproducts (RAGE), nucleotide binding oligomerisation domain (NOD)-like receptors (NLR), c-type lectin receptors (CLR), RIG-I-like receptors (RLR), and intra-cytosolic DNA sensors. The reciprocal action between PAMP and PRR triggers the release of inflammatory mediators that regulate the elimination of invasive pathogens. Damage-associated molecular patterns (DAMP) are endogenous constituents released from damaged cells that also have the ability to activate the innate immune response. An increase of RAGE expression levels on neurons, astrocytes, microglia, and endothelial cells could be responsible for the accumulation of αβ-amyloid in dementia and related to the chronic inflammatory state that is found in neurodegenerative disorders.

Highlights

The central nervous system (CNS) is protected by a complex barrier system; a broad diversity of virus, bacteria, fungi, and protozoa can gain access and cause illness [1,2]
Innate immune cells are activated by endogenous constituents that are released from damaged cells, such as high mobility group box-1 protein (HMGB1], nucleic acids, amyloid β, cytochrome c, uric acid crystals, adenosine 5′-triphosphate (ATP), members of S100 protein family, histones, advanced glycation end products (AGE), and heat shock protein (HSP)
Toll-like receptors (TLR) recognize molecular motifs that are expressed by pathogens or endogenous ligands released from damaged cells [15]

Summary

Introduction

The central nervous system (CNS) is protected by a complex barrier system; a broad diversity of virus, bacteria, fungi, and protozoa can gain access and cause illness [1,2]. The host immune response occurs when pathogens are identified by antigen-presenting cells. The reciprocal action between PAMP and PRR triggers the release of inflammatory mediators that regulate the response necessary to eliminate the invasive pathogens [10]. Damage to CNS during infection commonly involves pathogenic mechanisms and the innate immune host response [13,14].

Results

Conclusion