2006 Environmental Triggers
Could bacteria be responsible for triggering lupus?
Dr. Mattner thinks so.
With LRI funding, he has helped to confirm a long-held suspicion that certain bacterial or viral infections can elicit strong immune responses that prompt autoimmune illnesses such as lupus.
In May 2008’s Cell Host & Microbe, Dr. Mattner and co-authors illustrate how the common gut bacterium Novosphingobium triggers autoimmune liver disease in mice. They show how the bacterium, due to its unique cell wall antigens, activates specialized immune system white blood cells that provide help for autoreactive B cells.
When extended to humans, the findings imply that straightforward antibiotic treatments might prevent or halt the autoimmune process in genetically susceptible individuals.
Dr. Mattner also investigated the role of the bacterium in indirectly prompting a hallmark of lupus: the production of antibodies to double-stranded DNA (dsDNA).
“Infection of mice with Novosphingobium triggers the production of signature autoantibodies (ds-DNA, PDC E2) against antigens commonly found in lupus (SLE) and primary biliary cirrhosis (PBC),” Dr. Mattner explains.
c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infection. Pedra JH, Mattner J, Tao J, Kerfoot SM, Davis RJ, Flavell RA, Askenase PW, Yin Z, Fikrig E. Infect Immun. 2008 Jan;76(1):308-16. Epub 2007 Nov 12.
Liver autoimmunity triggered by microbial activation of natural killer T cells. Mattner J, Savage PB, Leung P, Oertelt SS, Wang V, Trivedi O, Scanlon ST, Pendem K, Teyton L, Hart J, Ridgway WM, Wicker LS, Gershwin ME, Bendelac A. Cell Host Microbe. 2008 May 15;3(5):304-15.
Regulatory roles for NKT cell ligands in environmentally induced autoimmunity. Vas J, Mattner J, Richardson S, Ndonye R, Gaughan JP, Howell A, Monestier M. Nat Chem Biol. 2007 Sep;3(9):559-64. Epub 2007 Jul 29.
Synthesis and evaluation of stimulatory properties of Sphingomonadaceae glycolipids. Long X, Deng S, Mattner J, Zang Z, Zhou D, McNary N, Goff RD, Teyton L, Bendelac A, Savage PB. J Immunol. 2008 Nov 15;181(10):6779-88.
Regulatory roles for NKT cell ligands in environmentally induced autoimmunity. Vas J, Mattner J, Richardson S, Ndonye R, Gaughan JP, Howell A, Monestier M. J Immunol. 2008 Nov 15;181(10):6779-88.
Identification of Cd101 as a Susceptibility Gene for Novosphingobium aromaticivorans-Induced Liver Autoimmunity. Mohammed JP, Fusakio ME, Rainbow DB, Moule C, Fraser HI, Clark J, Todd JA, Peterson LB, Savage PB, Wills-Karp M, Ridgway WM, Wicker LS, Mattner J. J Immunol. 2011 May 25. [Epub ahead of print]
Evidence That Cd101 Is an Autoimmune Diabetes Gene in Nonobese Diabetic Mice. Rainbow DB, Moule C, Fraser HI, Clark J, Howlett SK, Burren O, Christensen M, Moody V, Steward CA, Mohammed JP, Fusakio ME, Masteller EL, Finger EB, Houchins JP, Naf D, Koentgen F, Ridgway WM, Todd JA, Bluestone JA, Peterson LB, Mattner J, Wicker LS. J Immunol. 2011 May 25. [Epub ahead of print]
Dr. Mattner has been awarded an NIH grant for $1.875 million to expand on his work initially funded by the LRI.
Upon alerting the LRI to the five-year grant in the spring of 2009, Dr. Mattner explained it was “based on studies that were supported by the LRI where we investigated the role of NKT cells in breaking peripheral tolerance (discoveries published in Cell Host & Microbe)…in the new grant proposal we extended our research to the investigation of genetic factors that predispose for the development of severe organ specific pathology upon infection with Sphingomonas [a bacterium].”