Laboratory of Parasitic Diseases

Yasmine Belkaid, Ph.D.

Investigator
Chief, Mucosal Immunology Unit

Mucosal Immunology Unit

Description of Research Program

The Mucosal Immunology Unit¹s long-term interest is in understanding the immunologic mechanisms induced by parasites to promote survival within their hosts, with the goal of developing new intervention strategies. Our work has led us to believe that, in most parasitic diseases, the existence of regulatory elements is a better predictor of the outcome of infection than is the intensity of the effector response.

We have previously shown that specialized subsets of T cells, termed regulatory T cells (Treg), are involved in the control of infectious diseases. Treg have been shown to limit the magnitude of effector responses, resulting in failure to adequately contain infection. Moreover, Treg also help to limit collateral tissue damage caused by vigorous antimicrobial immune responses.The unit aims to elucidate mechanisms of immune regulation mediated by Treg during infection with unicellular parasites that invade the gut or the skin.

Both sites are major barriers, constantly exposed to both pathogenic and commensal microorganisms. The gut and the skin are highly regulated tissues that must generate both tolerogenic and immunogenic responses. The underlying hypothesis of the unit's research is that regulatory functions have to be dampened to maximize effector responses against pathogens.

Our current work proposes that targeting host regulatory mechanisms will both uncover and unleash potent effector functions against parasites. To address these issues, we are focusing our research on one dermal parasite (Leishmania major) and three gastrointestinal pathogens, Cryptosporidium and Microsporidium and Toxoplasma spp. Using these pathogens we are exploring the role, origin mechanism of action, and antigen presenting cell requirement of Treg that accumulate at sites of infection.

Research Group Members

From left to right: David Chou, Cheng Ming Sun, Sarah Ashrad, Nicolas Bouladoux, Rebecca Blank, Jason Hall and Yasmine Belkaid

Parasite-specific natural Treg in contact with L. major-infected dendritic cell

Selected Publications

(View list in PubMed.)

Belkaid Y. Regulatory T cell in infection: a dangerous necessity. Nature Immunology Review. 2007. October; 7(11): 875-88

Sun C, Hall J, Blank RB, Oukka M, Mora JR, Belkaid Y. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 Treg via retinoic acid. J. Exp. Med. 2007. 6;204(8):1775-85.

Suffia IJ, Reckling SK, Piccirillo CA, Goldszmid RS, Belkaid Y . Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens. J. Exp. Med. 2006 Mar 20;203(3):777-88.

Suffia I, Reckling SK, Salay G, Belkaid Y. A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection. J. Immunol.2005 May 1;174(9):5444-55.

Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease. Nat.Immunol. 2005 Apr 6; (4):353-60.

Mendez S, Reckling SK, Piccirillo CA, Sacks D, Belkaid Y. Role for CD4+CD25+ regulatory T cells in reactivation of persistent leishmaniasis andcontrol of concomitant immunity. J. Exp. Med. 2004 Jul 19;200:201-10.

Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 2002;420:502­7.

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