Infection by Schistosoma mansoni, a parasitic helminth, is a major health concern worldwide. Severe liver damage is the major consequence of schistosomiasis and results from the immune response to schistosomal eggs trapped in the liver. The following studies are designed to investigate the role of IL-6 during the early innate response induced by S. mansoni egg antigens and to look at how these responses direct the development of the adaptive immune response and affect target organ (liver) cells. During infection an early burst of the cytokine IL-4 occurs shortly after egg deposition and is believed to be crucial for subsequent Th2 response development. I will investigate whether or not this early IL-4 is produced by naive Th cells following stimulation by IL-6. Recent studies support a host-beneficial role for IL-4, since in its absence, infection leads to more severe liver damage. I postulate that at the site of egg deposition through the intestinal wall, LPS derived from the normal gut flora enters the bloodstream and influences the hepatic response to egg antigens. I propose that IL-4 is necessary to down-regulate the inflammatory responses to the LPS and SEA and thus prevent liver damage. In this context, I will investigate the responses of the resident cells in the liver (primary liver hepatocytes, endothelial cells, and macrophages) to SEA and LPS and determine whether IL-4 and IL-6 act directly on these cell types to lessen the liver damage that is associated with pro-inflammatory mediator production. Overall these studies are designed to understand the immune response to schistosome eggs and how that response can be modulated to reduce liver pathology during chronic S. mansoni infection.
| Patton, Elisabeth A; La Flamme, Anne C; Pedras-Vasoncelos, Joao A et al. (2002) Central role for interleukin-4 in regulating nitric oxide-mediated inhibition of T-cell proliferation and gamma interferon production in schistosomiasis. Infect Immun 70:177-84 |
| La Flamme, Anne Camille; Scott, Phillip; Pearce, Edward J (2002) Schistosomiasis delays lesion resolution during Leishmania major infection by impairing parasite killing by macrophages. Parasite Immunol 24:339-45 |
| Patton, E A; Brunet, L R; La Flamme, A C et al. (2001) Severe schistosomiasis in the absence of interleukin-4 (IL-4) is IL-12 independent. Infect Immun 69:589-92 |
| La Flamme, A C; MacDonald, A S; Pearce, E J (2000) Role of IL-6 in directing the initial immune response to schistosome eggs. J Immunol 164:2419-26 |
| La Flamme, A C; Pearce, E J (1999) The absence of IL-6 does not affect Th2 cell development in vivo, but does lead to impaired proliferation, IL-2 receptor expression, and B cell responses. J Immunol 162:5829-37 |
