Reinhard Hinterleitner, PhD

  • Assistant Professor, Department of Immunology

Education & Training

  • PhD in Immunology, Medical University Innsbruck (Austria), 2012
  • MS in Biotechnology, University of Applied Sciences Vienna (Austria), 2007

Research Interests

The Hinterleitner Lab studies mucosal immune responses to gut microbes. Current projects are centered around these two research topics:

1)   How do gut microbes shape immune responses in the context of celiac disease and food allergies?

Oral tolerance to dietary antigens is accomplished through the induction of peripheral-induced Foxp3+ regulatory T cells. Under tissue distress (e.g. virus infection) an undesired proinflammatory response to dietary antigens can be triggered leading to loss of oral tolerance (LOT). LOT sets the stage for developing celiac disease and food allergies. We have shown that enteric reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease (Science, 2017). We identified commensal gut microbes that promote oral tolerance to dietary antigens and prevent virus-mediated LOT. We are currently elucidating how these microbes modulate mucosal immune responses to dietary antigens in mouse models of celiac disease and food allergy by using state of the art tools including 20+ color flow cytometry, NextGen sequencing and metabolomics.

2)   What are the regulators of microbe-induced type-2 immunity in the intestine?

Intestinal type-2 immunity confer protection against parasitic microbes but also participate in inflammatory bowel disease (IBD). Our goal is to better understand the underlying mechanisms of microbe-induced type-2 immune responses that result in protective host responses but can also lead to IBD. To elucidate the regulatory mechanisms of gut microbial-induced type-2 immune responses we use NextGen sequencing to identify pathways and gene modules and functionally test them using CRISPR-engineered genetically modified mice, intestinal organoid co-cultures and various molecular biology-based approaches.

Publications

Hinterleitner R#, Meisel M#,  Pacis A, Chen L, Earley ZM, Mayassi T, Pierre JF, Ernest JD, Galipeau HJ, Thuille N, Bouziat R, Buscarlet M, Ringus DL, Wang Y, Li Y, Dinh V, Kim SM, McDonald BD, Zurenski MA, Musch MW, Furtado G, Lira S, Baier G, Chang EB, Eren MA, Weber CR, Busque L, Godley LA, Verdú EF, Barreiro LB and Jabri B. 2018. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature. 557: 580-584. #contributed equally

Bouziat R, Biering SB, Kouame E, Sangani K, Kang S, Ernest JD, Varma M, Brown JJ, Urbanek K, Dermody TS, Ng A, Hinterleitner R, Hwang S and Jabri B. 2018. Norovirus infection induces inflammatory responses to dietary antigens. Cell Host & Microbe. 24: 677-688.e5.

Hinterleitner R#, Bouziat R#, Brown JJ#, Stencel-Baerenwald JE, Ikizler M, Mayassi T, Meisel M, Kim SM, Discepolo V, Pruijssers AJ, Ernest JD, Iskarpatyoti JA, Costes LMM, Lawrence I, Palanski BA, Varma M, Zurenski MA, Khomandiak S, McAllister N, Aravamudhan P, Boehme KW, Hu F, Samsom JN, Reinecker HC, Kupfer SS, Guandalini S, Semrad C, Abadie V, Khosla C, Barreiro LB, Xavier RJ, Ng A, Dermody TS and Jabri B. 2017. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science. 356: 44-50. #contributed equally.

Pierre JF, Hinterleitner R, Bouziat R, Hubert NA, Leone V, Miyoshi J, Jabri B and Chang EB. 2017. Dietary antioxidant micronutrients alter mucosal inflammatory risk in a murine model of genetic and microbial susceptibility. J Nutr Biochem. 54: 95-104.

 

Hinterleitner R and Jabri B. A dendritic cell subset designed for oral tolerance. 2016. Nat Immunol. 17: 474-476.

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