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Therapeutic Boosting of the Immune Response: Turning to CD14 for Help.

ABSTRACT: The Toll-like family of immune receptors (TLRs) are critical for an efficient immune response to a variety of microorganisms and other antigens that may cause pathology. Modulating immune responses by targeting TLRs therefore has substantial therapeutic potential, and a number of TLR-based therapeutic strategies have been developed. Minimizing the adverse effects that may result from the therapeutic manipulation of these signalling receptors nevertheless remains a major challenge. Efficient responses via TLRs require the activity of the co-receptor CD14, which enhances TLR responses. In an attempt to boost the immune response for therapeutic purposes, we have sought to target CD14 to achieve TLR modulation. Here we discuss the design, activity and therapeutic development options of TLR-derived peptides that interact with CD14 and enhance its co-receptor activity, thus amplifying TLR-mediated responses. This strategy represents a promising alternative to current TLR-based therapies, as it has the potential to amplify responses to different pathogens mediated by different TLRs by targeting the common TLR co-receptor, CD14.

SUBMITTER: Raby AC

PROVIDER: S-EPMC5421138 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Therapeutic Boosting of the Immune Response: Turning to CD14 for Help.

Raby Anne-Catherine AC Labéta Mario O MO

Current pharmaceutical biotechnology 20160101 5

The Toll-like family of immune receptors (TLRs) are critical for an efficient immune response to a variety of microorganisms and other antigens that may cause pathology. Modulating immune responses by targeting TLRs therefore has substantial therapeutic potential, and a number of TLR-based therapeutic strategies have been developed. Minimizing the adverse effects that may result from the therapeutic manipulation of these signalling receptors nevertheless remains a major challenge. Efficient resp ...[more]

PMID: 26778454

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Project description:Transcriptomic profiling of the immune response induced by vaccine adjuvants is of critical importance for the rational design of vaccination strategies. In this study, transcriptomics was employed to profile the effect of the vaccine adjuvant used for priming on the immune response following re-exposure to the vaccine antigen alone. Mice were primed with the chimeric vaccine antigen H56 of Mycobacterium tuberculosis administered alone or with the CAF01 adjuvant and boosted with the antigen alone. mRNA sequencing was performed on blood samples collected 1, 2, and 7?days after priming and after boosting. Gene expression analysis at day 2 after priming showed that the CAF01 adjuvanted vaccine induced a stronger upregulation of the innate immunity modules compared with the unadjuvanted formulation. The immunostimulant effect of the CAF01 adjuvant, used in the primary immunization, was clearly seen after a booster immunization with a low dose of antigen alone. One day after boost, we observed a strong upregulation of multiple genes in blood of mice primed with H56?+?CAF01 compared with mice primed with the H56 alone. In particular, blood transcription modules related to innate immune response, such as monocyte and neutrophil recruitment, activation of antigen-presenting cells, and interferon response were activated. Seven days after boost, differential expression of innate response genes faded while a moderate differential expression of T cell activation modules was appreciable. Indeed, immunological analysis showed a higher frequency of H56-specific CD4+ T cells and germinal center B cells in draining lymph nodes, a strong H56-specific humoral response and a higher frequency of antibody-secreting cells in spleen of mice primed with H56?+?CAF01. Taken together, these data indicate that the adjuvant used for priming strongly reprograms the immune response that, upon boosting, results in a stronger recall innate response essential for shaping the downstream adaptive response.

Dataset Information

Therapeutic Boosting of the Immune Response: Turning to CD14 for Help.

Publications

Therapeutic Boosting of the Immune Response: Turning to CD14 for Help.

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