Pattern Recognition Receptors at the crosstalk between innate and adaptive immune systems and implications for vaccine development

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Background

Pattern Recognition Receptors (PRRs) are transmembrane or cytosolic glycoproteins expressed in a plethora of cell types but predominantly in cells of the innate immune system, such as macrophages and dendritic cells. Their role is to detect any loss of homeostasis in the body and "raise the alarm”. They do this by recognizing exogenous motifs that are highly conserved and frequently associated with pathogens, known as Pathogen-Associated Molecular Patterns (PAMPs), or endogenous molecules released upon tissue damage, known as Danger-Associated Molecular Patterns (DAMPs). Upon activation, PRRs initiate a cascade of signaling events that culminate into microbicidal and pro-inflammatory immune responses to eliminate, or at least to contain, the threat. Part of the pro-inflammatory response elicited by PRR activation in innate immune cells is the production of potent cytokines, such as TNF-α, IL-6, IL-12, IL-1β and IL-18.
The importance of this phenomenon is two-fold. Firstly, these cytokines provide key co-stimulatory signals during presentation of antigens by dendritic cells and macrophages to naïve T cells leading to their differentiation into the most appropriate subset of activated T cells to eliminate the pathogen. It appears, therefore, that PRR activation mediates the crosstalk between innate and adaptive immunity with the specific repertoire of PRRs expressed by antigen-presenting cells being key for the specificity of adaptive immune responses. Secondly, it raises the possibility of using PRR ligands as adjuvants in vaccine preparations. A few molecules have already attracted considerable interest over the last two decades, such as detoxified LPS recognised by Toll-like receptor 4, lipoproteins recognised by Toll-like receptor 2 and bacterial flagellin by Toll-like receptor 5. However, there is a fine balance between achieving beneficial adjuvanticity and causing catastrophic reactogenicity; for example excessive activation of Toll-like receptor 4 can cause endotoxic shock and sepsis. The rational criteria for achieving this balance have not been thoroughly investigated. However, the increase in the prevalence of multi-drug resistant bacterial pathogens and the need for better and rapid vaccines against emerging viral diseases continue to increase alarmingly fast. For these reasons, the development of alternative ways to combat infectious diseases is a matter of urgency.
This Research Topic proposes to gather data in order to understand better the interaction between pathogens, PRRs and pathogen-specific immunity together with the aim of exploring the safety and practicality of using PRR ligands as adjuvants which could facilitate the development of new vaccines with improved efficacy. At present, little is known, about whether and how specific PRRs influence the development of adaptive immunity and specifically that of immunological memory against pathogenic bacteria that is critical for vaccine development. Therefore, in this Research Topic we welcome the submission of Original Research, Methods, Perspective, Review or Mini-Review that cover, but not limited to, the following topics:

1. Role of PRR activation in vaccine adjuvanticity
2. Role of PRR activation in vaccine reactogenicity
3. Type of immunological response induced upon activation of different PRR
4. Role of pro-inflammatory cytokines on the specificity of adaptive immune responses.
5. Development of novel adjuvants

Topic editor Omar Rossi is employed by GSK. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: PRR activation, vaccine development, cytokines, adaptive immunity

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