Regulierung der Immunsuppression durch CD163 bei Pyelonephritis und chronischer lymphatischer Leukämie

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Pyelonephritis (PN) is a condition defined by bacterial invasion of the renal parenchyma. While most patients exhibit a mild course of the disease, a fraction of elderly, immunodeficient and cancer patients develops severe PN, requiring hospitalization. However, the mechanisms, which cause increased susceptibility to bacterial infections, leading to severe inflammation and impairment of kidney function are not understood. Innate immune cells, such as macrophages, employ a very broad phenotypical and functional repertoire and modulate critical anti-bacterial immune responses. The hemoglobin (Hb) scavenger receptor CD163 plays an essential role in macrophages polarization towards an anti-inflammatory state and has been implicated in different types of cancer and immunological disorders. Preliminary data revealed a highly significant upregulation of CD163 in the kidney of human patients suffering from severe PN. Through this proposal, we aim to study whether the expression of CD163 on macrophages predispose to severe PN through immunosuppression. We aim to (I) Deconvolute the spatial proteome to study macrophage polarization in human PN, (II) clarify the spatial mechanism for macrophage polarization in human PN, (III) evaluate the potential of soluble CD163 as a biomarker in blood and urine of PN patients, (IV) investigate the mechanism of immune suppression in CLL through CD163+ macrophages, and (V) clarify the role of CD163+ macrophages in PN.