Massachusetts General Hospital-East
Mucosal Immunology and Biology Research Center
Building 114 16th Street
Charlestown, MA 02129
Visit my lab page here.
Work in my laboratory is directed at understanding the factors that influence immune responses to bacterial enteropathogens. One of our current interests is in the role played by iron metabolism in host-pathogen interactions. Using Hfe knock-out mice, a model of human type I hemachromatosis, we have found that the dysregulation of iron homeostasis that is associated with this disorder influences the response to Salmonella typhimurium infection. Our observations suggest that abnormally low levels of intracellular free iron impair signaling downstream of the Toll-like receptor 4 in macrophages and compromise the expression of cytokines such as TNFα. As we try to clarify the mechanism of this effect further, we are also carrying out experiments to determine how infectious and inflammatory diseases alter host iron metabolism. We expect that these studies will lead to novel insights into the bidirectional cross-talk between the pathways that regulate iron homeostasis and the immune response and, ultimately, to new strategies for the therapeutic manipulation of these two processes.
Selected recent publications:
1. Chlosta S, Fishman DS, Harrington L, Johnson EE, Knutson MD, Wessling-Resnick M, Cherayil BJ. The iron efflux protein ferroportin regulates the intracellular growth of Salmonella enterica. Infect. Immun. 2006; 74: 3065-3067.
2. Wang L, Johnson EE, Shi HN, Walker WA, Wessling-Resnick M, Cherayil BJ. Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. J. Immunol. 2008; 181: 2723-2731.
3. Wang L, Harrington L, Trebicka E, Shi HN, Kagan JC, Hong CC, Lin HY, Babitt JL, Cherayil BJ. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis. J. Clin. Invest. 2009; 119: 3322-3328.
4. Wang L, Trebicka E, Fu Y, Waggoner L, Akira S, Fitzgerald KA, Kagan JC, Cherayil BJ. Regulation of lipopolysaccharide-induced translation of tumor necrosis factor α by the Toll-like receptor 4 adaptor protein TRAM. J. Innate Immun. 2011; 3: 437-446.
5. Shanmugam NKN, Ellenbogen S, Trebicka E, Wang L, Mukhopadhyay S, Gallini CA, Garrett WS, Lacy-Hulbert A, Cherayil BJ. TNFα inhibits expression of the iron regulating hormone hepcidin in murine models of innate colitis. PLoS One 2012; 7: e38136.
6. Trebicka E, Jacob S, Pirzai W, Hurley BP, Cherayil BJ. Role of anti-lipopolysaccharide antibodies in serum bactericidal activity against Salmonella enterica serovar Typhimurium in healthy adults and children in the United States. Clin Vaccine Immunol. 2013. In press.
For a complete listing of publications click here.
Last Update: 1/6/2014