Metaorganism Immunity Section
Yasmine Belkaid, Ph.D.
Chief, Metaorganism Immunity Section
Chief, Laboratory of Host Immunity and Microbiome
Contact: For contact information, search the NIH Enterprise Directory.
Major Areas of Research
- Role of the microbiota in immunity to infection
- Role of dietary metabolites in promoting immune regulation and immune responses to pathogens
- Tissue specific regulatory responses to infection
- Leishmania major, Toxoplasma gondii, Cryptosporidium and Microsporidium spp
Program Description
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.
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 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
For more about Dr. Belkaid's research, see The Microbiome: When Good Bugs Go Bad.
Biography
Education
Ph.D., 1996, Pasteur Institute, France
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.
Selected Publications
Harrison OJ, Linehan JL, Shih HY, Bouladoux N, Han SJ, Smelkinson M, Sen SK, Byrd AL, Enamorado M, Yao C, Tamoutounour S, Van Laethem F, Hurabielle C, Collins N, Paun A, Salcedo R, O'Shea JJ, Belkaid Y. Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury. Science. 2019 Jan 4;363(6422).
Linehan JL, Harrison OJ, Han SJ, Byrd AL, Vujkovic-Cvijin I, Villarino AV, Sen SK, Shaik J, Smelkinson M, Tamoutounour S, Collins N, Bouladoux N, Dzutsev A, Rosshart SP, Arbuckle JH, Wang CR, Kristie TM, Rehermann B, Trinchieri G, Brenchley JM, O'Shea JJ, Belkaid Y. Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair. Cell. 2018 Feb 8;172(4):784-796.
Han SJ, Glatman Zaretsky A, Andrade-Oliveira V, Collins N, Dzutsev A, Shaik J, Morais da Fonseca D, Harrison OJ, Tamoutounour S, Byrd AL, Smelkinson M, Bouladoux N, Bliska JB, Brenchley JM, Brodsky IE, Belkaid Y. White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection. Immunity. 2017 Dec 19;47(6):1154-1168.
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 Oct 8;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 Apr 2;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 Jan 24;343(6169):432-7.
Research Group
Victor Band, Ph.D.
IRTA Postdoctoral Fellow
Victor received his B.S. from Tufts University and his PhD from Emory University, where he studied antibiotic resistance within bacterial subpopulations to last line drugs. His current research interests include the metabolic responses of bacteria to antibiotics and the downstream immune response.
Nicolas Bouladoux, Ph.D.
Staff Scientist
Nicolas obtained his bachelor’s degree in cellular biology and his master’s degree in biochemistry and immunology from the Faculty of Science at Paris-Sud University in Orsay, France. He received his Ph.D. from Pierre and Marie Curie University in Paris, studying the intestinal immune responses against microsporidia, a group of opportunistic intracellular parasites causing gastrointestinal diseases in humans. His research focuses on understanding how different commensal species interact with the host immune system and how such interactions help protect the host from harmful pathogens.
Liang Chi, Ph.D.
Postdoctoral Visiting Fellow
Liang received his bachelor’s degree in biology from Lanzhou University, and completed his Ph.D. in University of North Carolina at Chapel Hill. His Ph.D. study investigated the health effects of environmental toxin-induced gut microbiota dysbiosis. His current research focuses on the crosstalk between microbiota and skin immunity.
Jeremie Delaleu, M.D.
Ph.D. Candidate
Jérémie received his M.D. from the Université Paris Cité and completed his residency in the great Paris University Hospitals as a dermatologist and a clinical immunologist. A Fellow of the European Academy of Dermatology and Venerology, he is currently working as a Ph.D. candidate in the Belkaid lab studying how the interaction between the immunity to the microbiota and the skin sensory neurons may affect inflammatory skin diseases.
Michel Enamorado, Ph.D.
Cancer Research Institute Irvington Postdoctoral Fellow
Michel received his B.S. in Biochemistry from University of Havana. He completed his Ph.D. research in the Immunobiology Laboratory at CNIC, and received his Ph.D. in Molecular Biosciences/Immunology from Autonomous University of Madrid in Spain. During his Ph.D., he studied the interaction between circulating and tissue-resident memory CD8+ T cells in tumor immunity. His current research at MIS focuses on understanding the generation of commensal-specific B and T cells, how they function and why they fail to induce long-term protective immunity.
Taylor Farley, B.S.
D.Phil Student, University of Oxford
Taylor received her B.S. in Microbiology from Colorado State University. Following her degree, she was awarded an NIH post-baccalaureate fellowship where she studied the role of a TNF superfamily member, TL1A, in multiple models of autoimmune disease. Currently, she is focusing her research on non-classical immunity to the microbiome in patients with inflammatory disorders.
Ana Teijeiro Garcia-Quijada, Ph.D.
Ana obtained her Bachelor’s degree in Biology and her Master’s degree in Genetics and Cell Biology at the Complutense University of Madrid in Spain. She received her Ph.D. in Molecular Biosciences from the Autonoma University of Madrid in Spain, studying the role of the Interleukin 17 A in obesity, metabolic syndrome and hepatocellular carcinoma in the laboratory of Dr. Nabil Djouder at the Spanish National Cancer Research Center (CNIO). Her current research aims to understand the role of the immune system in bone metastasis and how nutrition can impact tumor immunity.
Eduardo Ansaldo Gine, Ph.D.
IRTA Postdoctoral Fellow
Eduard received his B.S in Biotechnology from the Autonomous University of Barcelona. He went on to pursue his Ph.D at the University of California, Berkeley, in the laboratory of Gregory Barton, where he studied intestinal adaptive immune responses to the commensal bacterium Akkermansia muciniphila. As a postdoctoral fellow in LISB he is interested in understanding how early life exposures affect tissue-specific immunity.
Inta Gribonika, Ph.D.
Inta obtained a B.Sc. degree in biology from the University of Latvia (Riga, Latvia), working on virus-like particle nanotechnology in the lab of Prof. Kaspars Tars. She was awarded a Marie Curie ITN fellowship to pursue doctoral training in immunology with Prof. Nils Lycke at the University of Gothenburg (GU) (Göteborg, Sweden), where she studied mucosal immune responses to oral antigens. As a postdoctoral researcher, she then joined the lab of Prof. Jonas A Nilsson at Sahlgrenska Center for Cancer Research, GU, to focus on the epigenetic remodeling of uveal melanoma. Her current research in the Belkaid lab focuses on skin humoral immunity to commensal microbiota.
Siddharth Krishnamurthy, Ph.D.
IRTA Postdoctoral Fellow
Sidd received his BS/MS in Microbiology from the University of California, San Diego, and obtained his Ph.D. in Immunology at Washington University in Saint Louis, where he focused on creating novel computational methods to discover viruses and characterizing novel RNA phages. His current research in the Metaorganism Immunity Section focuses on understanding the role of the virome in immunity.
Pete Warakorn Kulalert, Ph.D.
Damon Runyon Cancer Research Foundation Postdoctoral Fellow
Pete received his bachelor's in 2010 from Harvard College and completed his PhD in 2017 from Massachusetts Institute of Technology. During his PhD, he studied neuroendocrine regulation of C. elegans development and stress physiology. His current research explores the neuroimmune interactions mediated by the skin microbiota.
Verena Link, Ph.D.
Bioinformatics Specialist
Verena received her bachelor’s and master’s degree in bioinformatics from the Ludwig Maximilian University of Munich and the Technical University of Munich. During her Ph.D. at the Ludwig Maximilian University of Munich she did her research in the laboratory of Dr. Chris Glass at the University of California, San Diego studying the effect of natural genetic variation on the epigenetic and transcriptional profile of murine macrophages. Her current research focuses on understanding how the microbiome influences the transcriptome and epigenome of a diverse set of immune cells.
Motoyoshi Nagai, Ph.D.
Motoyoshi received his B.S and Ph.D. in Pharmaceutical science from Keio University in Tokyo, focusing on the impact of fasting on mucosal immune response and immune cell dynamics. His current work will investigate the role of dietary factors in regulating wound healing processes.
Indira Rao, M.Sc.
Ph.D. Candidate, University of Pennsylvania-NIH GPP
Indira received her B.Sc. in Chemistry from the University of Mumbai, India, followed by her M.Sc. in Forensic Materials from Heriot-Watt University, UK. Currently, she is a PhD candidate with University of Pennsylvania and the NIH graduate partnership program. She is interested in delineating immunosurveillance mechanisms underlying muco-cutaneous microbial colonization to better understand the evolutionary arms race between the microbiome and its sapient host.
Claudia Rivera, Ph.D.
Claudia is originally from Chile. She received her BSc. from the Pontifical Catholic University of Chile with a major in Biochemistry. She then moved to Paris to complete her Ph.D. at Institut Curie, where she studied how subtissular niches promote functional diversification of dendritic cells in the laboratory of Dr. Ana-Maria Lennon-Duménil. She received her Ph.D. degree from Université Paris Cité. Her current research explores the impact of retroelements in gut immunity.
Elisha Segrist, Ph.D.
Elisha received her B.S. and B.A. with honors from Drury University in Chemistry and Biology. For her Ph.D. she joined the lab of Dr. Sara Cherry at the University of Pennsylvania. Her dissertation work focused on understanding how host sensing of the gut microbiota influences viral infection. She is currently investigating the mechanisms by which the local environment shapes immunity of the female reproductive tract.
Lillian Sun
Ph.D. Candidate
Lily is a MD/PhD student at the University of Pennsylvania. She completed her undergraduate studies at the University of Maryland, College Park with concentrations in Biology and Economics. Currently, she is interested in elucidating changes to skin immunity during pregnancy.
Alex Wells, Ph.D.
Cancer Research Institute Irvington Postdoctoral Fellow
Alex received her B.A. from New College of Florida with a major in Biology and a minor in Chemistry. She completed her Ph.D. at the University of Massachusetts, Amherst, where she studied the regulation of CD8 T cell differentiation by non-coding RNAs in the laboratory of Dr. Leonid Pobezinsky. Her current research aims to understand the molecular signals that regulate immunity in the skin.
Daniel Yong, B.A.
Daniel received his B.A. in Biology from the University of Chicago. He currently studies homeostatic immunity in the small intestine and the immune control of lactogenesis.
Patents
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.