Yasmine Belkaid, Ph.D.
Our laboratory aims to understand the mechanisms controlling host microbe interactions 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 tract, 2) dietary factors control the induction of effector and regulatory responses in the gut, 3) the gut compartment is a major site of induction of T cells and dendritic cells with regulatory functions, and 4) acute infections can have permanent consequences on tissue immunity.
Using a range of dermal and gastrointestinal pathogens (Leishmania sp., Cryptosporidium sp., Microsporidium sp., Toxoplasma sp., and Yersinia pseudotuberculosis) our laboratory currently further explores
- Function of the microbiota in the control of tissue immunity and pathogen infection
- Mechanism by which the microbiota control tissue immunity and inflammation
- Unique strategies developed by each tissue to maintain its integrity during inflammation
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.
Fonseca DM, Hand TW, Han SJ, Gerner MY, Glatman Zaretsky A, Byrd AL, Harrison OJ, Ortiz AM, Quinones M, Trinchieri G, Brenchley JM, Brodsky IE, Germain RN, Randolph GJ, Belkaid Y. Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity. Cell. 2015;163(2):354-66.
Naik S, Bouladoux N, Linehan JL, Han SJ, Harrison OJ, Wilhelm C, Conlan S, Himmelfarb S, Byrd AL, Deming C, Quinones M, Brenchley JM, Kong HH, Tussiwand R, Murphy KM, Merad M, Segre JA, Belkaid Y. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature. 2015;520(7545):104-8.
Spencer SP, Wilhelm C, Yang Q, Hall JA, Bouladoux N, Boyd A, Nutman TB, Urban JF Jr, Wang J, Ramalingam TR, Bhandoola A, Wynn TA, Belkaid Y. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science. 2014;343(6169):432-7.
Grainger JR, Wohlfert EA, Fuss IJ, Bouladoux N, Askenase MH, Legrand F, Koo LY, Brenchley JM, Fraser ID, Belkaid Y. Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat Med. 2013;19(6):713-21.
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.