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.
Immunofluorescent image of immune cells surrounding a hair follicle, enriched in commensal bacteria.
Commensal bacteria invade the surface of the small intestine during parasite infection.
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
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.
Front row (L-R):Elizabeth Wohlfert, Research FellowAmiko Uchida, HHMI ScholarYasmine Belkaid, Section ChiefMichael Askenase, Ph.D. Student, University of Pennsylvania-NIH partnershipSean Spencer, Ph.D. Student, University of Pennsylvania-NIH partnershipShruti Naik, Ph.D. Student, University of Pennsylvania-NIH partnership
Back row (L-R):John Grainger, Postdoctoral FellowChristoph Wilhelm, Postdoctoral FellowNicolas Bouladoux, Staff ScientistMichael Molloy, Postdoctoral FellowTimothy Hand, Postdoctoral Fellow
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 Jan 24;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 Jun;19(6):713-21.
Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, Deming C, Quimones 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 Aug 31;337(6098):1115-9.
Hand TW, Dos Santos LM, Bouladoux N, Molloy MJ, Pagan AJ, Pepper M, Maynard CL, Elson CO 3rd, Belkaid Y. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science. 2012 Sep 21;337(6101):1553-6.
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 Nov; 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 Mar 25; 34(3):435-47.
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Valenzuela JG, Belkaid Y, Kamhawi S, Sacks D, Ribeiro JMC, inventors; The Government of the United States of America as represented by the Secretary Department of Health and Human Services, assignee. Anti-arthropod vector vaccines, methods of selecting and uses thereof. United States patent US 7,964,576. 21 Jun 2011.
Valenzuela JG, Ribiero JMC, Kamhawi S, Belkaid Y, Fischer L, Audonnet JC, Milward F, inventors; The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services, Merial Limited, assignees. P. ariasi polypeptides, P. perniciosus polypeptides and methods of use. United States patent US 7,741,437. 22 Jun 2010.
Valenzuela JG, Belkaid Y, Kamhawi S, Sacks D, Ribeiro JMC, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Anti-arthropod vector vaccines method of selecting and uses thereof. United States patent US 7,388,089. 17 Jun 2008.
Last Updated July 03, 2014