Sepsis is a dysregulated host response to systemic infection that leads to immunologic dysfunction and organ damage. This dysregulated host response, termed the cytokine storm, is composed of both pro- and anti-inflammatory cytokines that are detrimental or beneficial to host survival, respectively. While early intervention has improved survival of the acute inflammatory event, approximately 20% of people still succumb to the cytokine storm. Frustratingly, >100 phase II and II clinical trials aimed at limiting pro-inflammatory cytokines have failed indicating a greater need to understand the cytokine storm in order to improve patient outcomes. Yet, even as survival of the septic event has increased, it has become apparent that septic patients experience a prolonged state of immunologic dysfunction, termed immunoparalysis, that reduces host capacity to respond to secondary infections. My thesis work focuses on NK cells to understand the interplay between cellular responses and the septic event, this is with respect to both how NK cells influence septic inflammation and how NK cells become impaired contributing to the immunoparalysis state.

Publications

Urban, SL, Jensen, IJ, Pewe, LL, Badovinac, VP, and Harty, JT (2020). Peripherally-induced brain tissue resident memory CD8 T cells mediate protection against CNS infections. Nature Immunology In Press (2020).

Jensen IJ, McGonagill PW, Lefebvre MN, Griffith TS, Harty JT, and Badovinac VP. Worry and FRET: ROS production leads to fluorochrome tandem degradation and impairs interpretation of flow cytometric results. Immunity 52(3), 419-421 (2020).

Huggins MA, Sjaastad FV, Pierson M, Kucaba TA, Swanson W, Staley C, Weingarden AR, Jensen IJ, Danahy DB, Badovinac VP, Jameson SC, Vezys V, Masopust D, Khoruts A, Griffith TS, Hamilton SE. Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization. Cell Rep. 2019 Aug 13;28(7):1729-1743.e5. doi:10.1016/j.celrep.2019.07.028. PubMed PMID: 31412243; PubMed Central PMCID:PMC6703181.

Espinosa-Cotton M, Fertig EJ, Stabile LP, Gaither-Davis A, Bauman JE, Schmitz S, Gibson-Corley KN, Cheng Y, Jensen IJ, Badovinac VP, Laux D, Simons AL. A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab. Biomark Res. 2019 Jul 16;7:14. doi:10.1186/s40364-019-0164-0. eCollection 2019. PubMed PMID: 31346466; PubMed Central PMCID: PMC6636109.

Martin MD, Jensen IJ, Ishizuka AS, Lefebvre M, Shan Q, Xue HH, Harty JT, Seder RA, Badovinac VP. Bystander responses impact accurate detection of murine and human antigen-specific CD8 T cells. J Clin Invest. 2019 Jun 20;130:3894-3908. doi: 10.1172/JCI124443. PubMed PMID: 31219804; PubMed Central PMCID: PMC6715387.

Danahy DB, Kurup SP, Winborn CS, Jensen IJ, Harty JT, Griffith TS, Badovinac VP. Sepsis-Induced State of Immunoparalysis Is Defined by Diminished CD8 T Cell-Mediated Antitumor Immunity. J Immunol. 2019 Aug 1;203(3):725-735. doi:10.4049/jimmunol.1900435. Epub 2019 Jun 12. PubMed PMID: 31189573; PubMed Central PMCID: PMC6650357.

Danahy DB, Jensen IJ, Griffith TS, Badovinac VP. Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival. J Immunol. 2019 May 15;202(10):2843-2848. doi:10.4049/jimmunol.1900076. Epub 2019 Apr 10. PubMed PMID: 30971442; PubMed Central PMCID: PMC6504616.

Espinosa-Cotton M, Rodman Iii SN, Ross KA, Jensen IJ, Sangodeyi-Miller K, McLaren AJ, Dahl RA, Gibson-Corley KN, Koch AT, Fu YX, Badovinac VP, Laux D, Narasimhan B, Simons AL. Interleukin-1 alpha increases anti-tumor efficacy of cetuximab in head and neck squamous cell carcinoma. J Immunother Cancer. 2019 Mar 19;7(1):79. doi: 10.1186/s40425-019-0550-z. PubMed PMID: 30890189; PubMed Central PMCID: PMC6425573.

Jensen IJ, Winborn CS, Fosdick MG, Shao P, Tremblay MM, Shan Q, Tripathy SK, Snyder CM, Xue HH, Griffith TS, Houtman JC, Badovinac VP. Polymicrobial sepsis influences NK-cell-mediated immunity by diminishing NK-cell-intrinsic receptor-mediated effector responses to viral ligands or infections. PLoS Pathog. 2018 Oct 31;14(10):e1007405. doi: 10.1371/journal.ppat.1007405. eCollection 2018 Oct. PubMed PMID: 30379932; PubMed Central PMCID: PMC6231673.

Jensen IJ, Sjaastad FV, Griffith TS, Badovinac VP. Sepsis-Induced T Cell Immunoparalysis: The Ins and Outs of Impaired T Cell Immunity. J Immunol. 2018 Mar 1;200(5):1543-1553. doi: 10.4049/jimmunol.1701618. Review. PubMed PMID:29463691; PubMed Central PMCID: PMC5826615.

Danahy DB, Anthony SM, Jensen IJ, Hartwig SM, Shan Q, Xue HH, Harty JT, Griffith TS, Badovinac VP. Polymicrobial sepsis impairs bystander recruitment of effector cells to infected skin despite optimal sensing and alarming function of skin resident memory CD8 T cells. PLoS Pathog. 2017 Sep 14;13(9):e1006569. doi:10.1371/journal.ppat.1006569. eCollection 2017 Sep. PubMed PMID: 28910403; PubMed Central PMCID: PMC5599054.

Jensen IJ, Li X, McGonagill PW, Shan Q, Fosdick MG, Tremblay MM, Houtman JC, Xue HH, Griffith TS, Peng W, Badovinac VP. Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells. Elife. 2021 Oct 15;10:e70989. doi: 10.7554/eLife.70989. PMID: 34652273; PMCID: PMC8589447.

Berton RR, McGonagil PW, Jensen IJ, Ybarra TK, Bishop, Harty JT, Griffith TS, Badovinac VP. Sepsis leads to lasting changes in phenotype and function of naive CD8 T cells. PLoS Pathog. 2023 Oct 12;19(10):e1011720. doi:10.1371journal.ppat.1011720.eCollection 2023 Oct. PMID 37824591