Primary Human Dendritic Cells and Whole-Blood Based Assays to Evaluate Immuno-Modulatory Properties of Heat-Killed Commensal Bacteria

There is mounting evidence that the microbiome plays a critical role in training and maturation of the host immune system. Pre-clinical and clinical studies have shown that microbiome perturbation is correlated with sub-optimal host responses to vaccines and cancer immunotherapy. As such, identifyin...

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Bibliographic Details
Published in:	Vaccines (Basel) Vol. 9; no. 3; p. 225
Main Authors:	Norton, Jr, James E, Kommineni, Sushma, Akrivoulis, Patricia, Gutierrez, Dario A, Hazuda, Daria J, Swaminathan, Gokul
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 05-03-2021 MDPI
Subjects:	Adenosine triphosphate Bacteria Blood Cancer immunotherapy Cancer vaccines CD80 antigen CD83 antigen Cell culture Cell differentiation Chemokines commensal bacteria Culture Cytokines Dendritic cells E coli Heat Histocompatibility antigen HLA host–microbiome interactions IL-1β immune modulation Immune system Immunology Immunomodulation Immunotherapy innate immunity Interleukin 1 Macrophage inflammatory protein 1 Maturation microbiome Microbiomes Modulators Monocytes Perturbation Strains (organisms) Vaccines United States > US dendritic cells commensal bacteria immune modulation host–microbiome interactions innate immunity microbiome
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Summary:	There is mounting evidence that the microbiome plays a critical role in training and maturation of the host immune system. Pre-clinical and clinical studies have shown that microbiome perturbation is correlated with sub-optimal host responses to vaccines and cancer immunotherapy. As such, identifying species of commensal bacteria capable of modulating immunological outcomes is of considerable interest. Currently, the lack of reliable primary immune cell-based assays capable of differentiating immuno-modulatory properties of various commensal bacteria is a major limitation. Here, we demonstrate that primary human monocyte-derived dendritic cells (MoDC) are capable of stratifying different strains of live and heat-killed commensal bacteria in an in vitro culture system. Specifically, heat-killed bacterial strains were able to differentially modulate co-stimulation/maturation markers CD80, CD83, and HLA-DR, as well as cytokine/chemokine signatures, such as IL-1b, MIP-1a, and TNFa in primary human MoDC. We further validated our observations using the TruCulture (Myriad RBM, Inc., Austin, TX, USA) whole-blood ex vivo culture system. Using this ex vivo system allowed us to measure immune-altering effects of commensal bacteria in primary human whole-blood. As such, we report that both these primary in vitro and ex vivo systems are robust and enable identification, stratification, and differentiation of various commensal bacteria as potential modulators of host immunity.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: Novartis Institute of Biomedical Research (NIBR), Cambridge, MA 02139, USA. Current address: TCR2 Therapeutics, Cambridge, MA 02142, USA.
ISSN:	2076-393X 2076-393X
DOI:	10.3390/vaccines9030225