Natallia successfully defended her thesis in September 2016!

Publications:

Salei N, Hellberg L, Köhl J, Laskay T. Enhanced survival of Leishmania major in neutrophil granulocytes in the presence of apoptotic cells. PLoS One. 2017 Feb 10;12(2):e0171850. doi: 10.1371/journal.pone.0171850. eCollection 2017. PubMed PMID: 28187163.

Project:

Clearance of dying inflammatory neutrophils by macrophages has a critical function for the resolution of the inflammatory response. Macrophages are, however, rare at sites of acute inflammation whereas the number of neutrophils within the tissue can be extremely high. Therefore, it is of importance that neutrophils can efficiently phagocytose apoptotic neutrophils. Importantly, the phagocytosis of apoptotic cells by neutrophils is anti-inflammatory. Lipoxins and resolvins have been shown to have broad counter-regulatory properties in vivo including a suppressive effect on both neutrophil-mediated and T-cell-mediated responses. On the other hand, deficient production of these lipids has been implicated in the pathogenesis of diverse inflammatory diseases. Of note, these mediators also upregulate the non-inflammatory ingestion of apoptotic neutrophils by macrophages. Thus, whether lipoxins and resolvins also modulate neutrophil-mediated clearance of apoptotic neutrophils remains to be defined. The ingestion of apoptotic cells by phagocytes, in addition to its role for the resolution of inflammation, contributes to the spread of certain intracellular pathogens such as Leishmania parasites. Understanding of the modulation of apoptotic cell clearance by lipid mediators can, therefore, provide novel insights into pathomechanisms of infectious processes.

Aims:

1. Assess the ability of lipoxins and resolvins to alter neutrophil phagocytosis of apoptotic neutrophils in vitro and in vivo.

2. Identify the signaling pathways central to neutrophil phagocytosis of apoptotic cells.

3. Define the in vivo significance of regarding i) the resolution of inflammation and ii) the effect on experimental cutaneous leishmaniasis.