This is of specific interest in infection because iron is an essential nutrient for most micro-organisms while on the other hand it exerts subtle effects on immune effector pathways specifically of macrophages. Accordingly, during an infection host derived cytokines and acute phase proteins affect the expression of central iron transport proteins to limit the availability of iron for microbes and to increase innate immune responses, which, however, leads to the development of anemia of inflammation.
The group of Weiss has recently demonstrated that macrophages targeted with viable Salmonella typhi-murium modify cellular iron homeostasis by increasing the expression of the iron export protein ferroportin, thereby limiting the availability of iron for intramacrophage bacteria and strengthening anti-microbial immune effector pathways. They could also show that several innate resistance genes, such as NRAMP-1, lipocalin-2 and iNOS, exert part of their protective effects via modulation of microbial iron availability and innate immune responses, and that several immune effector pathways appear to be interconnected in an attempt to reduce microbial iron availability and growth.
Strong collaborations with the groups of:
Würzner, Lass-Flörl, Haas, Grubeck-Loebenstein, Kronenberg, Marx-Ladurner
Mitterstiller AM, Haschka D, Dichtl S, Nairz M, Demetz E, Talasz H, Soares M, Einwallner E, Esterbauer H, Fang FC, Geley S, Weiss G. Heme oxygenase 1 controls early innate immune response of macrophages to Salmonella typhimurium infection. Cell Microbiol doi:10.1111/cmi.12578 (2016).
Nairz M, Ferring-Appel D, Casarrubea D, Sonnweber T, Viatte L, Schroll A, Haschka D, Fang FC, Hentze MW, Weiss G, Galy B. Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection. Cell Host Microbe 18(2): 254-61 (2015).
Tancevski I, Nairz M, Duwensee K, Auer K, Schroll A, Heim C, Feistritzer C, Hoefer J, Gerner RR, Moschen AR, Heller I, Pallweber P, Li X, Theurl M, Demetz E, Wolf AM, Wolf D, Eller P, Ritsch A, Weiss G. Fibrates ameliorate the course of bacterial sepsis by promoting neutrophil rectruitment via CXCR2. EMBO Mol Med 6: 810-20 (2014).
Sonnweber T, Nachbaur D, Schroll A, Nairz M, Seifert M, Demetz E, Haschka D, Mitterstiller AM, Kleinsasser A, Burtscher M, Trübsbach S, Murphy AT, Wroblewski V, Witcher DR, Mleczko-Sanecka K, Vecchi C, Muckenthaler MU, Pietrangelo A, Theurl I, Weiss G. Hypoxia induced downregulation of Hepcidin is mediated by platelet derived growth factor BB. Gut 63: 1951-9 (2014).
Nairz M, Schleicher U, Schroll A, Sonnweber T, Theurl I, Ludwiczek S, Talasz H, Brandacher G Moser PL, Muckenthaler MU, Fang FC, Bogdan C, Weiss G. Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection. J Exp Med 210: 855-873 (2013).
Nairz M, Schroll A, Moschen AR, Sonnweber T, Theurl M, Theurl I, Taub N, Jamnig C, Neurauter D, Huber LA, Tilg H, Moser PL, Weiss G. Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting NF-κB-inducible immune pathways. Immunity 34: 61-74 (2011).
Reinhard Würzner, M.D., Ph.D.