Michael C. Carroll

Program Head, Graduate Program in Immunology

Department of Pediatrics (Pathology)
The CBR Institute for Biomedical Research, Inc.
Harvard Medical School
800 Huntington Ave
Boston, MA 02115
Tel : 617-278-6660
Fax: 617-278-6655
e-mail:carroll@cbr.med.harvard.edu
7 Postdoctoral Fellows, 2 Graduate Students

My lab is interested in understanding the role of natural IgM and complement system in innate and acquired immunity and how they link the two systems via cell surface receptors. Innate immunity is the host's first line of defense in recognition and response to non-self. While it is often referred to as a primitive immune system (relative to acquired immunity), it includes serum proteins and receptors (such as Toll like receptors), which are highly specific for many pathogens (and certain self-antigens).

In acquired immunity, natural IgM and the complement system also play a critical role by identifying conserved antigens and marking them with a cleavage product of complement C3. Covalent attachment of this ligand to antigen is important for two reasons: (1) it enhances localization of the antigen to the lymphoid compartment; (ii) it provides a ligand for B cell co-receptor which is essential for an effective B cell response.

We focus on three main areas of basic research: (i) autoimmunity; (ii) inflammation; and (iii) host response to pathogens. Using genetic techniques, novel strains of mice bearing altered innate or acquired immunity are developed for study. Results from our studies of mouse models of systemic lupus erythematosus suggest that innate immunity is protective against autoimmune disease. The underlying mechanism, we believe, is due to a regulatory role of innate immunity on tolerance of B lymphocytes.

In an animal model of inflammation, we have identified an essential role for natural IgM and complement in promoting an acute attack on self-tissues following periods of ischemia. We refer to this phenomena as Òinnate autoimmunityÓ. These observations could explain a common mechanism for reperfusion injury-a life threatening disorder that follows myocardial infarction, stroke, general trauma or surgery. Finally, we are exploring a murine model of influenza to identify the cellular and molecular basis for complement enhancement of acquired immunity to this highly infections and lethal virus.

Papers & Publications:

Roozendaal R, Carroll MC. Emerging Patterns in Complement-Mediated Pathogen Recognition. Cell 2006; 29-32.

Zhang M, Lloyd MH, Grosjean SA, Kelly RA, Carroll MC, Entman ML. The role of natural igM in myocardial ischemia-reperfusion injury. JMCC 2006.

Zhang M, Alicot, EM, Chiu I, Verna N, Vorup-Jensen T, Kessler B, Shimaoka M., Moore FD, Jr. and Carroll MC. Identification of the target Self antigens in Reperfusion injury. J Exp Med 2006; 203(1); 141-152.

Barrington RA, Zhang M, Zhong X, Jonsson H, Holodick N, Cherukuri A, Pierce SK, Rothstein TL, Carroll MC. CD21/CD35 co-receptor signaling promotes B cell survival during primary immune responses. J Immunol 2005; 175(5):2859-67