Paper Inmunologia

Commissioned Review |

doi: 10.1111/j.1365-2796.2007.01821.x

Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors

B. Albiger1, S. Dahlberg2, B. Henriques-Normark2 & S. Normark2

From the 1Medical Microbiology, Department of Laboratory Medicine, Lund University, Malmo¨ ; and 2Swedish Institute for Infectious DiseaseControl and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna; Sweden

Abstract. Albiger B, Dahlberg S, Henriques-Normark B, Normark S (Lund University, Malmo¨ ; and Kar- olinska Institutet, Solna; Sweden). Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors (Commis- sioned Review). J Intern Med 2007; 261:511–528.

The innate immunity plays a critical role in host pro- tection against pathogens and it relies amongst others on pattern recognition receptors such as the Toll-like receptors (TLRs) and the nucleotide-binding oligome- rization domains proteins (NOD-like receptors, NLRs) to alert the immune system of the presence of inva- ding bacteria. Since their recent discovery less than a decade ago,both TLRs and NLRs have been shown to be crucial in host protection against microbial infections but also in homeostasis of the colonizing

microflora. They recognize specific microbial ligands and with the use of distinct adaptor molecules, they activate different signalling pathways that in turns trigger subsequent inflammatory and immune responses that allows a immediate response towards bacterialinfections and the initiation of the long- lasting adaptive immunity. In this review, we will focus on the role of the TLRs against bacterial infec- tions in humans in contrast to mice that have been used extensively in experimental models of infections and discuss their role in controlling normal flora or nonpathogenic bacteria. We also highlight how bacteria can evade recognition by TLRs.Keywords: toll-like receptors, innate immunity, bacter- ial injection.

Introduction

The human body is constantly exposed to microbes that usually only colonize the host harmlessly, but that may cause infectious diseases, sometimes leading to fatal outcomes. To control the resident colonizing microflora, as well as to fight pathogens, the human body has developed a variety of host defence mecha-nisms that in most cases effectively prevent the devel- opment of invasive microbial diseases. These defence mechanisms comprise physical or anatomical (skin, mucosal lining), mechanical (ciliated cells from the respiratory tracts, tight junctions) and biochemical barriers (tears or saliva containing antimicrobial lyso- zyme) as well as two inducible immune defence systems: the innate and theadaptive immune systems. These two systems are sequentially activated during

infection and work cooperatively to eradicate the microbial agent. The innate immune system is the first line of host defence towards microbial infections, whilst the adaptive immune system is elicited later, about 4–7 days postinfection and includes a specific and long-lasting immunity that is based on the rear- rangementand the clonal expansion of a random repertoire of antigen receptors (TCR and BCR) on lymphocytes. In this review, we will focus on the early innate responses and the role of the Toll-like receptors (TLRs).

The innate immune system gives protection to a broad variety of pathogens and is based on a limited reper- toire of germline-encoded receptors called pattern recognition receptors (PRRs)because they recognize conserved microbial components known as

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pathogen-associated molecular patterns (PAMPs). The PRRs include amongst others the members of the TLRs family and the nucleotide-binding oligomeriza- tion domain proteins (NOD-like receptors, NLRs) [1, 2]. Here, we will primarily discuss the role of TLRs in host protection...