Elsevier

Seminars in Immunology

Volume 27, Issue 2, March 2015, Pages 119-124
Seminars in Immunology

Review
Dendritic cell functions: Learning from microbial evasion strategies

https://doi.org/10.1016/j.smim.2015.03.012Get rights and content

Highlights

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    Microorganisms can interfere with recognition, antigen processing and presentation, and killing by macrophages and dendritic cells.

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    Each pathogenic microorganism has developed unique strategies to evade APC recognition.

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    Understanding how microorganisms evade the immune response can shed light on how APCs interact with microorganisms.

Abstract

Dendritic cells (DCs) are specialized antigen presenting cells (APC) that are fundamental to initiate both immunity and tolerance. DCs play a ‘sentinel’ role to protect our body from potential pathogens and induce tolerogenic responses toward harmless antigens. The flexibility of DCs or macrophages to adapt to the environment and to respond accordingly can be hijacked by pathogens for their own interest to transform a potentially immunogenic APC into a tolerogenic cell with clear consequences in pathogen clearance. While these immune evasion mechanisms can be detrimental for the host, they can highlight important molecular pathways in DCs necessary for their function. In this review we will mention several mechanisms employed by pathogens to evade DC patrolling function.

Introduction

Dendritic cells (DCs) are specialized antigen presenting cells (APC) that are fundamental to initiate both immunity and tolerance [1]. DCs are located at the interfaces between our body and the external world [2]. Here they play a ‘sentinel’ role to protect our body from putative aggressors [3], [4], but they can also induce tolerogenic responses toward harmless antigens [5]. Interestingly, the different function of DCs is dictated by several factors, including the ‘polarization’ obtained in the tissue of origin [6], their maturation state [7], the subset of analyzed DCs and macrophages [8] and the encounter with different external cues [9].

The characteristic of DCs or macrophages to quickly adapt to changes in the microenvironment renders them particularly susceptible to pathogens that can interfere with APC flexibility and transform the functionality of these cells to their own interest [10].

While these immune evasion mechanisms can be detrimental for the host, they can highlight important molecular pathways in dendritic cells necessary for their function. In this review, we will discuss several mechanisms employed by pathogens to evade DC patrolling function. These evasion mechanisms can affect antigen uptake, survival within phagolysosomes, antigen processing and presentation, DC maturation and cytokine production. This review is intended to give an overview on the different strategies adopted by pathogens rather than being an exhaustive analysis on all the different microbes capable of evading the immune surveillance by antigen presenting cells.

Section snippets

The family of APCs

APCs are fundamental to orchestrate the immune response to pathogens and to establish tolerance to harmless antigens. These complex tasks are accomplished by a whole family of APCs, whose function differ according to the tissue of origin [4]. APC subsets derive from bone marrow progenitors that seed peripheral organs or secondary lymphoid tissues where they receive instructions that make these cells ‘specialized’ for that particular organ or tissue [3], [4]. Hence, APC subsets with shared

Mechanisms of evasion of bacterial recognition

DCs are alerted of the presence of pathogens via the binding of microbe-associated molecular patterns (MAMPs) to specialized pattern recognition receptors (PRR). PRRs are a family of receptors that include Toll-like receptors (TLR), nucleotide-binding site and leucine-rich repeat containing receptors (NLR) and retinoic acid inducible gene-I (RIG)-like receptors (RLR) (for a comprehensive review see [22]). The binding of MAMPs to PRR results in DC activation and release of immune modulators.

Exploitation of APC surface receptors

Chemokine receptors are used by APCs to migrate in response to chemokine gradients. CCR5 is a common chemokine receptor expressed on myeloid cells. Some bacteria and viruses use CCR5 to enter host cells. HIV-1 gp120 V3 loop binds to CCR5 and allows viral entry in CCR5+ cells, including DCs [34]. The binding to CCR5 can also be used by bacterial toxins to target immune cells. Staphylococcus aureus lukotoxin ED (LukED) induces killing of both macrophages and dendritic cells via a CCR5-dependent

Pathogens, phagocytosis and autophagy

DCs and macrophages are naturally phagocytic cells. They internalize microorganisms and initiate a process leading to their intracellular elimination. In the gut, APCs do not simply capture the antigen after epithelial cell trancytosis but can also directly sample the gut luminal content, via the extension of dendrites between epithelial cells [38] in the proximal small intestine [39]. CX3CR1+ macrophages can capture bacteria [40], soluble proteins [41] and fungi [42], while CD103+ DCs are not

Pathogens, DC maturation and T-cell activation

DC progenitors or inflammatory monocytes reach the tissues and secondary lymphoid organs where they differentiate into cells capable of responding to inflammation and infection. In order to become potent APCs, DCs undergo a process of maturation whereby they up-regulate the expression of co-stimulatory and MHC molecules and release a set of cytokines that dictate the outcome of T-cell activation. It was initially thought that immature DCs drive tolerogenic response, while mature DCs drive

Mechanisms controlling cell death

The encounter of pathogens with APCs often results in the death of the latter via an apoptotic mechanism. In this way infected cells die and do not allow the replication of the pathogen. Some pathogens have developed strategies to change the death modality from apoptosis to necrosis. The latter allows the bacteria to spread and disseminate to other neighboring cells [72]. Necrosis and apoptosis are regulated by different signaling pathways. PGE2 is a pro-apoptotic mediator that protects

Conclusions

In conclusion, pathogens have evolved many strategies to evade the immune response, from phagocytosis to antigen processing and presentation (Fig. 1). Some pathogens have developed also strategies on multiple pathways so to inhibit the initiation of immunity or to promote the development of tolerance at several levels. Understanding how pathogens evade the immune response gives hints on how the immune response is initiated and provides new tools to interfere with microbial survival within the

Conflict of interest

The author declare that there is no conflict of interest.

Acknowledgements

This work is supported by grants of the European Commission (7th Framework program: ERC-Dendroworld and HomeoGUT); by the Italian Ministry of Health (Ricerca finalizzata) .

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