Innate immune mechanisms and the identification of immune potentiators as vaccine adjuvants

Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood.

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Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽

10.3390/pathogens10060675 ◽

2021 ◽

Vol 10 (6) ◽

pp. 675

Author(s):

Samira Elmanfi ◽

Mustafa Yilmaz ◽

Wilson W. S. Ong ◽

Kofi S. Yeboah ◽

Herman O. Sintim ◽

...

Keyword(s):

Immune Response ◽

Periodontal Disease ◽

Innate Immune ◽

Host Cells ◽

Type I Interferons ◽

Type I ◽

Vaccine Adjuvants ◽

Cyclic Dinucleotides ◽

Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

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319 The role of TLR-3 in the itch-scratch cycle of nodular prurigo - new insights into innate immune mechanisms of peripheral itch sensitization

Journal of Investigative Dermatology ◽

10.1016/j.jid.2016.06.339 ◽

2016 ◽

Vol 136 (9) ◽

pp. S215

Author(s):

A.G. Szollosi ◽

I. McDonald ◽

I.L. Szabó ◽

B. Kirby ◽

E. van den Bogaard ◽

...

Keyword(s):

Innate Immune ◽

Immune Mechanisms

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Periodontal innate immune mechanisms relevant to atherosclerosis

Molecular Oral Microbiology ◽

10.1111/omi.12087 ◽

2014 ◽

Vol 30 (3) ◽

pp. 171-185 ◽

Cited By ~ 10

Author(s):

S. Amar ◽

M. Engelke

Keyword(s):

Innate Immune ◽

Immune Mechanisms

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An integrated view of innate immune mechanisms in C. elegans

Biochemical Society Transactions ◽

10.1042/bst20210399 ◽

2021 ◽

Author(s):

Benjamin W. Harding ◽

Jonathan J. Ewbank

Keyword(s):

Innate Immune ◽

Innate Immune Responses ◽

Fully Integrated ◽

Immune Mechanisms ◽

C Elegans ◽

Cellular Processes ◽

Physiological Processes ◽

Model Animal ◽

Molecular Specificity ◽

Simple Notion

The simple notion ‘infection causes an immune response' is being progressively refined as it becomes clear that immune mechanisms cannot be understood in isolation, but need to be considered in a more global context with other cellular and physiological processes. In part, this reflects the deployment by pathogens of virulence factors that target diverse cellular processes, such as translation or mitochondrial respiration, often with great molecular specificity. It also reflects molecular cross-talk between a broad range of host signalling pathways. Studies with the model animal C. elegans have uncovered a range of examples wherein innate immune responses are intimately connected with different homeostatic mechanisms, and can influence reproduction, ageing and neurodegeneration, as well as various other aspects of its biology. Here we provide a short overview of a number of such connections, highlighting recent discoveries that further the construction of a fully integrated view of innate immunity.

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