Erik Brincks

Roles for TRAIL in the Immune Response to Influenza Virus Infection

My research examines the role that TNF-related apoptosis inducing ligand (TRAIL) plays in the immune response to influenza infection. Classically, roles for TRAIL have been in the context of tumor immunology, where interactions of TRAIL with its ligand DR-5 (TRAIL-R2) stimulate apoptosis in tumor cells. Recent studies have suggested a role for TRAIL signaling in the immune response to viral infections—including RSV, HSV, and HIV. Our preliminary studies of influenza infection in TRAIL-deficient mice show increased disease severity compared to TRAIL-sufficient mice. My goals are to determine the role that TRAIL is playing in the immune response to influenza virus infections and to elucidate the cause of the increased disease severity in the TRAIL -/- mice.

Brincks EL, Kucaba TA, James BR, Murphy KA, Schwertfeger KL, Sangwan V, Banerjee S, Saluja AK, Griffith TS. Triptolide enhances the tumoricidal activity of TRAIL against renal cell carcinoma. FEBS J. 2015 Dec;282(24):4747-65. doi:10.1111/febs.13532. PubMed PMID: 26426449; PubMed Central PMCID: PMC4715782.

Cabrera-Perez J, Condotta SA, James BR, Kashem SW, Brincks EL, Rai D, Kucaba TA, Badovinac VP, Griffith TS. Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge. J Immunol. 2015 Feb 15;194(4):1609-20. doi: 10.4049/jimmunol.1401711. Epub 2015 Jan 16. PubMed PMID: 25595784; PubMed Central PMCID: PMC4412277.

James BR, Anderson KG, Brincks EL, Kucaba TA, Norian LA, Masopust D, Griffith TS. CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma. Cancer Immunol Immunother. 2014 Nov;63(11):1213-27. doi: 10.1007/s00262-014-1598-8. Epub 2014 Aug 21. PubMed PMID: 25143233; PubMed Central PMCID: PMC4412276.

James BR, Brincks EL, Kucaba TA, Boon L, Griffith TS. Effective TRAIL-based immunotherapy requires both plasmacytoid and CD8α dendritic cells. Cancer Immunol Immunother. 2014 Jul;63(7):685-97. doi: 10.1007/s00262-014-1548-5. Epub 2014 Apr 8. PubMed PMID: 24711083; PubMed Central PMCID: PMC4058344.

Rodrigue-Gervais IG, Labbé K, Dagenais M, Dupaul-Chicoine J, Champagne C, Morizot A, Skeldon A, Brincks EL, Vidal SM, Griffith TS, Saleh M. Cellular inhibitor of apoptosis protein cIAP2 protects against pulmonary tissue necrosis during influenza virus infection to promote host survival. Cell Host Microbe. 2014 Jan 15;15(1):23-35. doi: 10.1016/j.chom.2013.12.003. PubMed PMID: 24439895.

Brincks EL, Risk MC, Griffith TS. PMN and anti-tumor immunity--the case of bladder cancer immunotherapy. Semin Cancer Biol. 2013 Jun;23(3):183-9. doi:10.1016/j.semcancer.2013.02.002. Epub 2013 Feb 11. Review. PubMed PMID: 23410637.

Steinwede K, Henken S, Bohling J, Maus R, Ueberberg B, Brumshagen C, Brincks EL, Griffith TS, Welte T, Maus UA. TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice. J Exp Med. 2012 Oct 22;209(11):1937-52. doi: 10.1084/jem.20120983. Epub 2012 Oct 15. PubMed PMID: 23071253; PubMed Central PMCID: PMC3478925.

Brincks EL, Gurung P, Langlois RA, Hemann EA, Legge KL, Griffith TS. The Magnitude of the T Cell Response to a Clinically Significant Dose of Influenza Virus Is Regulated by TRAIL. J Immunol. 2011 Sep 21. [Epub ahead of print] PubMed PMID: 21940678 PMCID:PMC3197947

Griffith TS, Brincks EL, Gurung P, Kucaba TA, Ferguson TA. Systemic immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells. J Immunol. 2011 Jan 15;186(2):791-8. Epub 2010 Dec 17. PubMed PMID:21169546; PubMed Central PMCID: PMC3075597.

Griffith TS, Stokes B, Kucaba TA, Earel JK Jr, VanOosten RL, Brincks EL, Norian LA. TRAIL gene therapy: from preclinical development to clinical application. Curr Gene Ther. 2009 Feb;9(1):9-19. Review. PubMed PMID: 19275567; PubMed Central PMCID: PMC2727705.

Brincks EL, Katewa A, Kucaba TA, Griffith TS, Legge KL. CD8 T cells utilize TRAIL to control influenza virus infection. J Immunol. 2008 Oct 1;181(7):4918-25. Erratum in: J Immunol. 2008 Nov 15;181(10)7428. PubMed PMID: 18802095; PubMed Central PMCID: PMC2610351.

Brincks EL, Kucaba TA, Legge KL, Griffith TS. Influenza-induced expression of functional tumor necrosis factor-related apoptosis-inducing ligand on human peripheral blood mononuclear cells. Hum Immunol. 2008 Oct;69(10):634-46. Epub 2008 Aug 22. PubMed PMID: 18723061; PubMed Central PMCID: PMC2597454.

Brincks, EL, Legge KL, Griffith TS (2008). TRAIL deficiency increases the severity of influenza virus infections. Options for the Control of Influenza VI. 158. (non peer reviewed therefore no PMCID)

Translational Research
Lumos Pharma
Erik Brincks