Department of Pathology
University of Iowa
Iowa City, IA 52242
Bachelor of Science in Biology - University of North Dakota
NK and NKT cells are major producers of inflammatory cytokines early after infection and help in the fight against pathogens before the adaptive immune system develops. Sepsis itself is essentially a massive infection characterized by hyperinflammatory state that is rapidly followed by immunosuppressive (hypoinflammatory) state. This initial deluge of cytokines, which NK and NKT cells undoubtedly contribute to, leads to severe lymphopenia and decreased functionality of the surviving cells. Extended impacts for the patients that survive septic episode are also a consideration as they may experience a state of immunosuppression for several years after the initiating septic event. This impairment seems to be largely restricted to lymphoid derived cells.
However, the majority of work on the lymphoid impairment has been focused on the impact of sepsis on CD4 and CD8 T cells. Meanwhile, its effects on NK and NKT cells remain largely understudied. In the context of sepsis, the majority of studies involve depleting NK and NKT subsets and examining how the absence of these cells impact host response (including survival) post sepsis induction. These studies have largely implicated NK and NKT cells as being deleterious during a septic event as mice survive better in their absence. However, because of the contribution NK and NKT cells could make toward control of pathogens, the state of immune suppression following sepsis indicates a more complex relationship of these cells with disease progression and recovery. Therefore, I will be evaluating the impact of sepsis on NK and NKT compartment, using the cecal ligation and puncture (CLP) mouse model of sepsis.
Given the current state of the field, our first steps will be to evaluate the numerical and functional alterations in circulating (PBL, spleen) and tissue (liver) NK and NKT populations at various times after CLP surgery. To do this I will be using several techniques to attain a more comprehensive understanding of how sepsis affects these cells. For evaluating functionality of cells I will determine expression of activating and inhibitory receptors such as (NKG2D and NKG2A, respectively). In addition, the ability of NK cells in a septic host to develop into memory-like cells will be investigated by defining Ly49H specific NK cell responses after MCMV infection. Alternatively, I will use the same system to address the extent to which sepsis influences pre-existing MCMV-specific memory NK cell responses. Finally, comprehensive analysis of transcriptional alterations in NK and NKT cells post sepsis will be defined by RNAseq in CLP and Sham (control) groups of mice. These characterization steps should greatly inform and direct future research and greatly expand our understanding of sepsis on NK and NKT populations.
- Urban SL, IJ Jensen, Q Shan, LL Pewe, HH Xue, VP Badovinac, and JT Harty. Peripherally induced brain tissue-resident memory CD8 T cells mediate protection against CNS infection. Nat Immunol 8: 938-949 (2020) [PubMed]
- Jensen IJ, PW McGonagill, MN Lefebvre, TS Griffith, JT Harty, and VP Badovinac. Worry and FRET: ROS production leads to fluorochrome tandem degradation annd impairs interpretation of flow cytometric results. Immunity 52: 419-421 (2020) [PubMed]
- Espinosa-Cotton M, EJ Fertig, LP Stabile, AG Davis, JE Bauman, S Schmitz, KN Gibson-Corley, Y Cheng, IJ Jensen, VP Badovinac, D Laux, and AL Simons. A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab. Biomark Res 7: 14 (2019) [PubMed]
- Huggins MA, FV Sjaastad, M Pierson, TA Kucaba, W Swanson, C Staley, AR Weingarden, IJ Jensen, DB Danahy, VP Badovinac, SC Jameson, V Vezys, D Masopust, A Khortus, TS Griffith, and SE Hamilton. Microbial exposure enhances immunity to pathogens recognized by TLR2 but increases susceptibility to cytokine storm via TLR4 sensitization. Cell Rep 28: 1729-1743 (2019) [PubMed]
- Danahy DB, IJ Jensen, TS Griffith, VP Badovinac. Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival. J Immunol 202: 2843 (2019) [PubMed]
- Espinosa-Cotton M, SN Rodman Iii S, KA Ross, IJ Jensen, K Sangodeyi-Miller, AJ McLaren, RA Dahl, KN Gibson-Corley KN, AT Koch, YX Fu, VP Badovinac, D Laux, B Narasimhan, AL Simons . Interleukin-1 alpha increases anti-tumor efficacy of cetuximab in head and neck squamous cell carcinoma. J Immunother Cancer 7:79 doi: 10.1186/s40425-019-0550-z. (2019) [PubMed]
- Danahy DB, SP Kurup, CS Winborn, IJ Jensen, JT Harty, TS Griffith, VP Badovinac. Sepsis-Induced State of Immunoparalysis Is Defined by Diminished CD8 T Cell-Mediated Antitumor Immunity. J Immunol 203: 725-735 (2019) [PubMed]
- Martin MD, IJ Jensen, AS Ishizuka, M Lefebvre, Q Shan, HH Xue, JT Harty, RA Seder, VP Badovinac. Bystander responses impact accurate detection of murine and human antigen-specific CD8 T cells. J Clin Invest 130: 3894-3908 (2019) [PubMed]
- Jensen IJ, CS Winborn, MG Fosdick, P Shao, MM Tremblay, Q Shan, SK Tripathy, CM Snyder, HH Xue, TS Griffith, JC Houtman, VP Badovinac. Polymicrobial sepsis influences NK-cell-mediated immunity by diminishing NK-cell-intrinsic receptor-mediated effector responses to viral ligands or infections. PLoS Pathog 14:10 (2018) [PubMed]
- Jensen IJ, FV Sjaastad, TS Griffith, VP Badovinac. Sepsis-Induced T Cell Immunoparalysis: The Ins and Outs of Impaired T Cell Immunity. J Immunol 200: 1543-1553. (2018) [PubMed]
- Danahy DB, SM Anthony, IJ Jensen, SM Hartwig, Q Shan, HH Xue, JT Harty, TS Griffith, and VP Badovinac. 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 13: 9 (2017) [PubMed]