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Spielmann, G.

Publications and source records attributed to Spielmann, G..

2 recordsLinked to original sources

Blood Biochemical Responses to Acute Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

Exercise benefits numerous organ systems and tissues, however limited knowledge exists about its underlying molecular pathways. Identifying the exercise-induced biochemical changes that occur in the circulation may provide further insights into how exercise confers systemic health changes. Here, we perform large-scale plasma proteomic, metabolomic, and whole blood transcriptional profiling in sedentary human participants undergoing acute endurance exercise (EE), resistance exercise (RE), or a non-exercise control (CON) in up to 7 timepoints over a 24 hour period. We observe 7066 transcript, 189 protein, and 448 metabolite changes in response to EE or RE compared to CON. Our analyses reveal numerous shared biochemical responses between EE and RE modes, but also differences in immune cell responses, lipid metabolism, and pathways reflective of tissue repair and angiogenesis. Taken together, our findings highlight novel temporal and exercise mode-specific blood-based molecular responses to acute exercise, and provide a new resource for the scientific community.

systems biology↗

RIG-I-like receptor-dependent type I Interferon regulates antigen dose and activation in yellow fever vaccine 17D-infected antigen presenting cells

The live-attenuated yellow fever vaccine 17D-204 (YF17D) activates robust innate immune responses followed by rapid induction of adaptive immunity resulting in long-lasting protection. YF17D triggers the production of type I interferons (IFNs) which have a dual role in antigen presenting cells regulating their infection and contributing to their activation. Infection with YF17D was detected in primary human blood monocytes and conventional dendritic cells (DCs) and in monocyte-derived DCs but was highly restricted by type I IFN. Blocking IFNAR signaling in YF17D-infected PBMC from vaccinated donors resulted in increased activation of YF17D-specific CD8+ T cells. Consistently, peak IFN-alpha plasma levels correlated inversely with the CD8+ T cells response in YF17D vaccinees. Loss of function experiments demonstrated a dominant role of retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and mitochondrial antiviral signaling protein (MAVS) for type I IFN induction and restriction of YF17D. The type I IFN response was mediated by 5 tri- or diphosphate dsRNA intermediates that are formed during YF17D infection. In vivo proximity labelling (IPL) of RIG-I and next-generation sequencing confirmed interaction of RIG-I with YF17D-dsRNA in infected cells. Thus, YF17D-triggered RLR-signaling restricts viral replication through type I IFN and thus limits the production of viral antigens that can be presented to T cells.

immunology↗