Bohdan Holoborodko (Regensburg / DE), Valentin Schatz (Regensburg / DE), Flora Weber (Dortmund / DE), Katja Dettmer (Regensburg / DE), Anika Grüneboom (Dortmund / DE), Jonathan Jantsch (Köln / DE)
In infected or inflamed tissues, low oxygen (O2) levels prevail, affecting the O2-dependent antimicrobial effectors of professional phagocytes, thereby promoting the survival of the intracellular parasite Leishmania (L.) major. However, the mechanism causing the local O2 deficiency in the infected lesion is unknown. The focus of this study is to determine the microenvironmental factors associated with low tissue O2 levels in the L. major lesions as well as to assess the contribution of these factors on lesional tissue O2 and host defense.
Using non-invasive O2 and perfusion measurement in a C57BL/6 (healer) / BALB/c (non-healer) mouse model, we demonstrate that the course of infection has a bi-phasic discrimination. The first phase is characterized by formation of the lesion. While the size of the lesion as well as oxygen levels remains indistinguishable between the strains, C57BL/6 animals exhibited elevated perfusion during this phase. In the second phase, the healer strain displays normalization of tissue oxygenation with increased tissue perfusion levels. In contrast, non-healer strain present a non-resolving course of infection without normalization of oxygen levels and only minimal changes in tissue perfusion.
Furthermore, by infecting T and B lymphocyte deficient (Rag2-KO) C57BL/6 mice, we investigated the contribution of the adaptive immune system in this context. These showed a similar non-healing course with a minimal increase in perfusion as BALB/c mice, but with a time delay in terms of lesion formation and decrease in oxygen levels.
Our data suggest that the adaptive immune response is involved in early oxygen depletion in infected tissues. We will use this experimental setup to uncover immunovascular crosstalk and its impact on host defense in the future.