Immune cell responses to inflammatory stimuli

Analysis of patient blood leukocytes

Systemic inflammation due to sterile or infectious tissue injury elicits an increase in both pro- and anti-inflammatory markers in blood. Peripheral blood leukocytes may carry information on the differential regulation of the host response with diagnostic value. To reveal such information, we analyze phenotypic, transcriptional, and functional changes in immune cells isolated from patients diagnosed with sepsis.

Support

This work is supported by the Klaus Tschira Stiftung within the SCIDATOS research alliance.

Inflammatory hypoxia

Natural killer (NK) cells are innate immune cells that contribute to both initiation and resolution of inflammation. Sustained low oxygen availability (hypoxia) inhibits NK cell effector functions, but little is known on the functional consequences of short term hypoxia. We found that global transcriptional NK cell responses in vitro to short term hypoxia relied largely on interleukin 15 (IL-15) priming, especially, for the hypoxia inducible factor 1 (HIF-1) signaling and glycolysis pathways. Hypoxia and priming cooperated in glycolytic switching at the transcriptional level. Hypoxia promoted chemokine secretion (Ccl3/4/5 and MIF) and migration through extracellular matrix, and shifted amounts of susceptible leukemia target cells toward late apoptosis. These features of hypoxically conditioned NK cells may be beneficial for their use in immunotherapy of cancer.

Publications

Velásquez SY, Coulibaly A, Sticht C, Schulte J, Hahn B, Sturm T, Schefzik R, Thiel M, Lindner HA. Key Signature Genes of Early Terminal Granulocytic Differentiation Distinguish Sepsis From Systemic Inflammatory Response Syndrome on Intensive Care Unit Admission.
Front Immunol. 2022;13:864835.
Abstract on Pubmed

Coulibaly A, Velásquez SY, Kassner N, Schulte J, Barbarossa MV, Lindner HA. STAT3 governs the HIF-1α response in IL-15 primed human NK cells.
Sci Rep. 2021;11(1):7023.
Abstract on PubMed

Lindner HA, Velásquez SY, Thiel M, Kirschning T.
Lung protection vs. infection resolution: interleukin 10 suspected of double-dealing in COVID-19.
Front. Immunol. 2021;12:602130.
Abstract on PubMed

Velásquez SY, Himmelhan BS, Kassner N, Coulibaly A, Schulte J, Brohm K, Lindner HA.
Innate cytokine induced early release of IFNγ and CC chemokines from hypoxic human NK cells is independent of glucose.
Cells. 2020;9(3):734.
Abstract on PubMed

Coulibaly A, Bettendorf A, Kostina E, Figueiredo AS, Velásquez SY, Bock HG, Thiel M, Lindner HA, Barbarossa MV.
Interleukin-15 signaling in HIF-1α regulation in natural killer cells, insights through mathematical models.
Front. Immunol. 2019;10:2401.
Abstract on PubMed

Coulibaly A, Velásquez SY, Sticht C, Figueiredo AS, Himmelhan BS, Schulte J, Sturm T, Centner FS, Schöttler JJ, Thiel M, Lindner HA.
AKIRIN1: A potential new reference gene in human natural killer cells and granulocytes in sepsis.
Int. J. Mol. Sci. 2019;20(9). pii: E2290.
Abstract on PubMed

Figueiredo AS, Killian D, Schulte J, Sticht C, Lindner HA.
Whole transcriptome data of primary human NK cells under hypoxia and interleukin 15 priming:
A 2×2 factorial design experiment.
Data Brief. 2017;14:77-83.
Abstract on PubMed

Velasquez SY, Killian D, Schulte J, Sticht C, Thiel M, Lindner HA. 2016. Short Term Hypoxia Synergizes with Interleukin 15 Priming in Driving Glycolytic Gene Transcription and Supports Human Natural Killer Cell Activities. J Biol Chem 291: 12960-12977.
Abstract on PubMed