Marco Colonna, MD
My laboratory studies human and murine innate responses against pathogens. Cells involved in innate responses use different types of receptors to recognize pathogens and tumors. Pattern recognition receptors recognize molecular structures shared by disparate microorganisms. Activating receptors recognize "alert molecules" that are only expressed when cells are infected or transformed. Inhibitory receptors recognize MHC class I molecules or other molecules constitutively expressed in normal cells. When infection and neoplastic transformation cause reduction of MHC class I, inhibitory receptors are no longer engaged, releasing innate responses from inhibition.
We have discovered the KIR and ILT receptors that allow natural killer cells, monocytes, macrophages and dendritic cells (DC) to detect infected cells with reduced levels of MHC class I molecules. More recently we have characterized the TREM receptors that trigger inflammatory responses of granulocytes and monocytes and activate DC. We are presently investigating the ligands of TREM receptors as well as their function in vivo.
We have also found that DC differ in the type ofILTreceptors expressed on the cell surface. This observation has led to the identification of a subset of DC called plasmacytoid DC or natural interferon-producing cells (IPC). IPC are specialized in the production of interferon-á, â and ù, providing a first line of defense against viral replication and promoting Th1 polarization of T helper cells. We are currently studying the role of IPC in viral infections using in vivo models.
- Bouchon A, Hernandez-Munain C, Cella M, Colonna M.. A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells.. J Exp Med 194:1111-1122, 2001 Abstract
- Bouchon A, Facchetti F, Weigand MA, Colonna M.. TREM-1 amplifies inflammation and is a crucial mediator of septic shock.. Nature 410:1103-1107, 2001 Abstract
- Cella M, Facchetti F, Lanzavecchia A, Colonna M.. Blood plasmacytoid dendritic cells mature upon stimulation with influenza virus and CD40L and drive a potent Th1 polarization.. Nat Immunol 1:305-310, 2000 Abstract
- Dietrich J, Cella M, Seiffert M, Buhring HJ, Colonna M.. Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells.. J Immunol 164:9-12, 2000 Abstract
- Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, Colonna M.. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon.. Nat Med 5:919-923, 1999 Abstract
- Colonna M, Navarro F, Bellón T, Llano M, García P, Samaridis J, Angman L, Cella M, López-Botet M.. A Common Inhibitory Receptor for MHC Class I Molecules on Human Lymphoid and Myelomonocytic Cells.. J Exp Med 186:1809-1818, 1997 Abstract
- Cella M, Dohring C, Samaridis J, Dessing M, Brockhaus M, Lanzavecchia A, Colonna M.. A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing.. J Exp Med 185:1743-1751, 1997 Abstract
- Colonna M, Samaridis J.. Cloning of Immunoglobulin-Superfamily Members Associated with HLA-C and HLA-B Recognition by Human NK Cells.. Science 268:405-408, 1995 Abstract
- Colonna M, Spies T, Strominger JL, Ciccone E, Moretta A, Moretta L, Pende D, Viale O.. Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene.. Proc Natl Acad Sci USA 89:7983-7985, 1992 Abstract
DBBS Graduate Program Affiliation