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LAWRENCE L. JOHNSON, PH.D.
Innate and acquired immunity to infection.

My lab employs the protozoan parasite Toxoplasma gondii to study innate host defense mechanisms as well as acquired immunity and vaccination. We are also investigating the mechanisms underlying immunopathology caused by infection.

T. gondii is a ubiquitous parasite that causes potentially devastating infection in the infected fetus and in adults with compromised immune systems. Infections in immunocompetent adults are usually mild, however. After parasites are ingested, infection spreads acutely from the intestine to liver, lungs, and other organs, ultimately settling into a chronic infection after several weeks typified by numerous encysted organisms in the CNS. We and others have shown that during acute infection, innate immune mechanisms are critical for host survival. These mechanisms involve IL-12, interferon-gamma, and natural killer cells. In some strains of mice, such as C57BL/6, these early defense mechanisms may cause significant immunopathology resulting in collateral damage to vital host tissues such as the intestine and liver. This does not occur in other mouse strains such as BALB/c.

We are currently studying the underlying causes of this difference, as well as the proximal causes and consequences of the various manifestations of immunopathology.  We are especially interested in T cells that express Foxp3 or CTLA-4, molecules associated with regulatory functions.
 
Intact immune defenses are also required for successful control of chronic infections. There is a clear requirement for T lymphocytes and interferon-gamma, and we have recently demonstrated that B cells and the antibodies they produce are also a vital component of resistance during chronic infection. Our lab is actively investigating the role of B cells and antibodies in protection against oral reinfection in mice that have been vaccinated with an attenuated strain of T. gondii.

We also are studying the role of B cells in protecting the fetus from infection in vaccinated mothers that are reexposed to parasites during pregnancy.
 
We have shown that mice infected with T. gondii as neonates are very poorly protected against a later challenge with virulent parasites, whereas infected adults acquire strong protective immunity to a challenge infection. This finding has led us to study how adult mice vaccinated as neonates differ from adult-vaccinated adults in their ability to acquire and later express immunity to T. gondii.
 
Our laboratory uses a variety of contemporary cellular and molecular immunological techniques and collaborates extensively with other research laboratories within the Trudeau Institute.  In collaboration with Dr. Stephen Smiley, we have used the T. gondii model to study the protective role of fibrin deposition during infection and to dissect pathways involved in regulation of protective and pathological fibrin deposition. In collaboration with Dr. Markus Mohrs, we have used the T. gondii infection model to study interferon-gamma production at the single T cell level during infection.

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ROBERT NORTH, PH.D. MARCIA A. BLACKMAN, PH.D. TIMOTHY SELLATI, PH.D. LAWRENCE L. JOHNSON, PH.D. ANDREA COOPER, PH.D. ELIZABETH LEADBETTER, PH.D. ALEXEI TUMANOV, M.D., PH.D. JR-SHIUAN LIN, PH.D. WILLIAM W. REILEY, PH.D. RON GOLDFARB, PH.D. SUSAN L. SWAIN, PH.D. RICHARD W. DUTTON, PH.D. DAVID WOODLAND, PH.D. GARY WINSLOW, PH.D. LAURA HAYNES, PH.D.