Our research topics
Testicular infections by uropathogenic bacteria
Toll-like receptors recognize conserved microbial structures like lipopolysaccharides or peptidoglycans and activate signaling pathways that result in innate immune responses against microbial infections. The so-called "immunological privilege" of the testis is believed to arise from the need to prevent immune responses against auto-antigens of meiotic and haploid germ cells, which first appear in the testis at the time of puberty, long after the establishment of self-tolerance in the perinatal period. Paradoxically, the testis has an active defense mechanism that is illustrated by the obvious capacity for inflammatory responses to local and systemic infection. However, the testicular defense to infection, particularly to bacteria, is poorly defined on the molecular level. The aim of our studies is to define the essential targets involved in bacterial infection of the testis.
MIF Projekt
The macrophage migration inhibitory factor (MIF) was first described in 1966 as a T-cell derived cytokine playing a pivotal role during inflammation. Within the last ten years MIF was found to be expressed by most organs and tissues, so that its functions cannot be restricted to the immune system. We found that the factor is synthesized and released by Leydig cells and acts as a paracrine mediator in the regulation of testicular function. By employing an interactome screen we discovered a ribosomal protein that appears to limit MIF’s proinflammatory function. Furthermore, with the aid of two other interaction partners, MIF is regulating the ubiquitin/proteasome system of the cell. Our main goal is to find out the mechanisms by which MIF and its entourage of interacting proteins is regulating vital cellular functions.
Experimental autoimmune orchitis
There is a considerable body of clinical evidence suggesting that the testis is compromised during illness or infection. Disruption of normal testicular function can lead to a decrease of serum testosterone levels and/or lower sperm counts. Depending on the extent of the impairment of steroidogenesis and/or spermatogenesis, fertility can be either temporarily or permanently compromised. The mechanisms underlying this inhibition are poorly understood.
Experimental autoimmune orchitis (EAO) is the principal animal model used to study noninfectious testicular inflammatory disease. Classical EAO, induced by the inoculation of a testicular homogenate and adjuvant, is characterized by inflammatory infiltrates in the testis (orchitis), epididymis (epididymitis), and vas deferens (vasitis).
Our studies investigate how immune cells (dendritic cells and macrophages), and the expression of different pro- and anti-inflammatory mediators, are involved in the pathomechanism underlying autoimmune testicular inflammation.