Jantsch, Jonathan - B 05

Endothelial cells and pericytes in cutaneous leishmaniasis

Prof. Dr. Jonathan Jantsch
Prof. Dr. Jonathan Jantsch

Institute for Medical Microbiology, Immunology and Hygiene

CMMC - PI - B 05

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed

Institute for Medical Microbiology, Immunology and Hygiene

Goldenfelsstraße 19-21

50935 Cologne

Introduction

Sufficient tissue oxygenation critically contributes to tissue homeostasis.  Moreover, oxygen is an important substrate for antimicrobial effector enzymes such as the inducible (type 2) nitric (NO) synthase or the phagocyte oxidase.
We use a murine model of cutaneous leishmaniasis to address the bidirectional interplay of tissue oxygenation and antimicrobial control. We have revealed that Leishmania skin lesions display low oxygen levels and that macrophages activated under these oxygen tensions fail to produce sufficient amounts of leishmanicidal NO to clear Leishmania. Resolution of disease requires normalization of lesional tissue oxygenation which is linked to enhanced tissue perfusion. In this project we would like to assess the contribution of pericytes and endothelial cells in normalizing tissue oxygenation and in resolution of disease.

Fig. 1: Cutaneous lesional tissue oxygen levels (pO2) and clinical course upon infection of C57BL/6 (healer mice) with Leishmania (L.) major. At low pO2 levels the type 2 (inducible) NO synthase in macrophages (MΦ) does not produce sufficient amounts of leishmanicidal NO to clear infection.

Clinical Relelevance

Leishmaniasis belongs to the neglected tropical diseases. It is a chronic and notoriously difficult to treat disease. In this proposal we aim to identify new adjunctive therapeutic vascular targets for the treatment of cutaneous leishmaniasis. Moreover, these findings will shed new light on the bidirectional immunovascular crosstalk in infectious disease in general and might be useful for treating other (chronic) infections and inflammatory conditions as well.

Approach

  • Transcriptional profiling of endothelial cells and pericytes during resolution
  • Targeting of pericytes and vascular signal transduction using transgenic approaches
Fig. 2: This project will test the contribution of pericytes and endothelial signal transduction in resolution of cutaneous leishmaniasis. We hypothesize that both cell types contribute to the normalization of tissue oxygen tension which enables production of leishmanicidal NO by mononuclear phagocytes and ultimately results in resolution of disease. Created with BioRender.com

Publication Record on PubMed - Jonathan Jantsch

2024 (up to June)
  • Li B, Thebault P, Labat B, Ladam G, Alt V, Rupp M, Brochausen C, Jantsch J, Ip M, Zhang N, Cheung WH, Leung SYS, and Wong RMY (2024). Implants coating strategies for antibacterial treatment in fracture and defect models: A systematic review of animal studies. J Orthop Translat45, 24-35. doi:10.1016/j.jot.2023.12.006.
     
  • Miyauchi H, Geisberger S, Luft FC, Wilck N, Stegbauer J, Wiig H, Dechend R, Jantsch J, Kleinewietfeld M, Kempa S, and Muller DN (2024). Sodium as an Important Regulator of Immunometabolism. Hypertension81, 426-435. doi:10.1161/HYPERTENSIONAHA.123.19489.
     
  • Proff A, Nazet U, Schroder A, and Jantsch J (2024). Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts. Cells13. doi:10.3390/cells13060496.
     
  • Radvanyi Z, Yoo EJ, Kandasamy P, Salas-Bastos A, Monnerat S, Refardt J, Christ-Crain M, Hayashi H, Kondo Y, Jantsch J, Rubio-Aliaga I, Sommer L, Wagner CA, Hediger MA, Kwon HM, Loffing J, and Pathare G (2024). Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation. J Biol Chem300, 105480. doi:10.1016/j.jbc.2023.105480.
2023
  • Deschner J, Schroder A, Weber M, Galler K, Proff P, Kirschneck C, Bozec A, and Jantsch J (2023). Advancing oral immunology for improving oral health. J Orofac Orthop. doi:10.1007/s00056-023-00473-3.
     
  • Hadrian K, Musial G, Schonberg A, Georgiev T, Kuper C, Bock F, Jantsch J, Cursiefen C, Eming SA, and Hos D (2023). The role of the osmosensitive transcription factor NFAT5 in corneal edema resorption after injury. Exp Mol Med 55, 565-573. doi:10.1038/s12276-023-00954-w.
     
  • Krampert L, Ossner T, Schroder A, Schatz V, and Jantsch J (2023). Simultaneous Increases in Intracellular Sodium and Tonicity Boost Antimicrobial Activity of Macrophages. Cells 12. doi:10.3390/cells12242816.
     
  • Miyauchi H, Geisberger S, Luft FC, Wilck N, Stegbauer J, Wiig H, Dechend R, Jantsch J, Kleinewietfeld M, Kempa S, and Muller DN (2023). Sodium as an Important Regulator of Immunometabolism. Hypertension. doi:10.1161/HYPERTENSIONAHA.123.19489.
     
  • Radvanyi Z, Yoo EJ, Kandasamy P, Salas-Bastos A, Monnerat S, Refardt J, Christ-Crain M, Hayashi H, Kondo Y, Jantsch J, Rubio-Aliaga I, Sommer L, Wagner CA, Hediger MA, Kwon HM, Loffing J, and Pathare G (2023). Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation. J Biol Chem 300, 105480. doi:10.1016/j.jbc.2023.105480.

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