Immunobiology

Jochen Mattner, MD

Title

Assistant Professor

Email

Jochen.Mattner@cchmc.org

Phone

513-803-0768

Bio

Dr. Mattner's laboratory studies the role of NKT cells during microbial infection and the impact of their activation on the immune response.
Recently, we could identify self and microbial glycosphingolipid (GSL) ligands that trigger NKT cell activation. This observation led to the characterization of two general modes of NKT cell activation during microbial infection. One pathway involves recognition of endogenous antigen(s) upregulated through TLR signaling by gram-negative LPS-positive bacteria like Salmonella. The other involves direct recognition of microbial GSLs, the LPS substitutes in Sphingomonas and related alphaproteobacteria suggesting that NKT cells represent a major innate recognition pathway for this class of bacteria.

Based on recent compelling evidence that patients with Primary Biliary Cirrhosis (PBC) are seropositive for Sphingomonas and exhibit NKT cell redistribution to the liver, we could establish a mouse model of infection-triggered autoimmunity of the liver. As our previous work had identified microbial glycosphingolipid (GSL) ligands in the cell wall of Sphingomonas that trigger NKT cell activation (see above) and as the development of liver disease was CD1d dependent, we concluded that exposure to Sphingomonas facilitates the production of auto-antibodies against PBC antigens and the induction of auto-reactive T cells due to NKT cell help. In that context, the preferential activation of NKT cells in the liver, where NKT cells are abundant and Sphingomonas preliminarily persists, may explain the biased autoreactivity towards autoantigens exposed in the liver environment and, ultimately, the severe organ-specific manifestations of Sphingomonas infection.

The major focus of the laboratory is now to explore the intriguing possibility that some forms of autoimmune PBC may be triggered by infection with Sphingomonas or related bacteria.

Credentials

MD: University of Erlangen, Erlangen, Germany, 2001

Postdoc Scholar: University of Chicago, Department of Pathology, 2003-2005

Research Associate / Assistant Professor: Department of Pathology, 2006-2007

Awards and Honors

AAI Young Faculty Award, 2007
Fritz - und - Ursula - Melchers price, 2006
ECIS travel grant award, 2006
Keystone travel grant award, 2005
CRI grant award, 2005-2007

Publications, Most Recent

Liu Y, Deng S, Bai L, Freigang S, Mattner J, Teyton L, Bendelac A, Savage PB. Synthesis of diglycosylceramides and evaluation of their iNKT cell stimulatory properties.Bioorg Med Chem Lett 2008;Jan 1:[Epub ahead of print].

Pedra JH, Mattner J, Tao J, Kerfoot SM, Davis RJ, Flavell RA, Askenase PW, Yin Z, Fikrig E. c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infection.Infect Immun 2008;76:308-16.

Rocha FJ, Schleicher U, Mattner J, Alber G, Bogdan C. Cytokines, signaling pathways, and effector molecules required for the control of Leishmania (Viannia) braziliensis in mice.Infect Immun 2007;75:3823-33

Long X, Deng S, Mattner J, Zang Z, Zhou D, McNary N, Goff RD, Teyton L, Bendelac A, Savage PB. Synthesis and evaluation of stimulatory properties of Sphingomonadaceae glycolipids.Nat Chem Biol 2007;3:559-64.

Liu Y, Goff RD, Zhou D, Mattner J, Sullivan BA, Khurana A, Cantu C. 3rd, Ravkov EV, Ibegbu CC, Altman JD, Teyton L, Bendelac A, Savage PB. A modified alpha-galactosyl ceramide for staining and stimulating natural killer T cells.J Immunol Methods 2006;312:34-9.

Sagiv Y, Hudspeth H, Mattner J, Schrantz N, Stern R, Zhou D, Savage PB, Teyton L, Bendelac A. Cutting Edge: Impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein.J Immunol 2006;177:26-30.

Mattner J, DeBord KL, Goff RD, Cantu III C, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin N, Hoebe K, Schneewind O, Ismail N, Walker D, Beutler B, Teyton L., Savage PB, Bendelac A. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections.Nature 2005;434:525–9.

Zajonic DM, Cantu III C, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L. Structure and function of a potent -galactosylceramide agonist for the semi-invariant NKT cell receptor.Nature Immunology 2005;6:810-8.

Mattner J, Donhauser N, Werner - Felmayer G, Bogdan C. NKT cells mediate organ-specific resistance against Leishmania major infection.Microbes Infect 2006;8:354-62.