Yasmine Belkaid, Ph.D.
Our laboratory aims to understand the mechanisms controlling infection at barrier sites such as the skin and the gut. These two sites represent the first portal of pathogen exposure and are major anatomical sites for development of inflammatory disorders. The skin and the gut also represent highly specialized environments with distinct structures, cell types, and innate defense mechanisms tailored to support their individual challenges. These include their exposure to factors from the outside environment, to dietary antigens, and to antigens derived from resident commensals. In particular, all barrier surfaces are covered by a diverse and abundant microbiota that play a dominant role in host physiology and immunity. However, this symbiotic relationship also poses a constant threat to the host, and aberrant reactivity against commensals can lead to life-threatening tissue damage. These conflicting pressures present the host system that defends the skin or the gut with unique challenges: tolerating constant exposure to innocuous antigens while simultaneously maintaining the capacity to rapidly respond to encounters with pathogens.
Because of the inherent complexity of these challenges, understanding how the immune system functions at barrier sites needs to be addressed in an integrated and multidisciplinary manner. In this context, our work has demonstrated that 1) commensals play a major role in the control of host defense in both the skin and the gastrointestinal (GI) tract, 2) dietary factors control the induction of effector and regulatory responses in the GI tract, and 3) in order to protect tissue integrity, the GI tract is a major site of induction of T cells and dendritic cells with regular functions.
Using a range of dermal and gastrointestinal pathogens (Leishmania sp., Cryptosporidium sp., Microsporidium sp., and Toxoplasma sp.), in tandem with a state of the art germ-free facility, our current work explores
- The function of the microbiota in the control of pathogen infection; specifically, characterizing the mechanisms by which dermal or gut commensals control immunity and pathology to infections
- The role of food-derived metabolites in the control of immunity and regulatory responses to pathogens; more particularly, assessing how vitamin metabolites control lymphocyte and dendritic cell functions in tissues
- The unique strategies developed by each tissue to maintain its integrity during inflammation; exploring the factors controlling the function of mucosal dendritic cells and macrophages, as well as the conditions favoring the induction and stability of regulatory T cells at barrier sites
Dr. Yasmine Belkaid obtained her Ph.D. in 1996 from the Pasteur Institute in France on innate responses to Leishmania infection. Following a postdoctoral fellowship at NIAID on immune regulation during Leishmania infection, she joined the Children's Hospital Research Foundation in Cincinnati as an assistant professor in 2002. In 2005, she joined the Laboratory of Parasitic Diseases as a tenure-track investigator. Since 2008, she has worked as an adjunct professor at the University of Pennsylvania._
Hand TW, Dos Santos LM, Bouladoux N, Molloy MJ, Pagán AJ, Pepper M, Maynard CL, Elson CO 3rd, Belkaid Y. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science. 2012;337(6101):1553-6.
Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, Deming C, Quinones M, Koo L, Conlan S, Spencer S, Hall JA, Dzutsev A, Kong H, Campbell DJ, Trinchieri G, Segre JA, Belkaid Y. Compartmentalized control of skin immunity by resident commensals. Science. 2012;337(6098):1115-9.
Wohlfert EA, Grainger JR, Bouladoux N, Konkel JE, Oldenhove G, Ribeiro CH, Hall JA, Yagi R, Naik S, Bhairavabhotla R, Paul WE, Bosselut R, Wei G, Zhao K, Oukka M, Zhu J, Belkaid Y. GATA3 controls Foxp3⁺ regulatory T cell fate during inflammation in mice. J Clin Invest. 2011;121(11):4503-15.
Hall JA, Cannons JL, Grainger JR, Dos Santos LM, Hand TW, Naik S, Wohlfert EA, Chou DB, Oldenhove G, Robinson M, Grigg ME, Kastenmayer R, Schwartzberg PL, Belkaid Y. Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity. 2011;34(3):435-47.
Maric I, Robyn J, Metcalfe DD, Fay MP, Carter M, Wilson T, Fu W, Stoddard J, Scott L, Hartsell M, Kirshenbaum A, Akin C, Nutman TB, Noel P, Klion AD. KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities. J Allergy Clin Immunol. 2007;120(3):680-7.