Christina Steel

Publications

• 2.84

  Impact points

  Distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the CNS.

  Christina D Steel, Woong-Ki Kim, Larry D Sanford, Laurie L Wellman, Sandra Burnett, Nico Van Rooijen, Richard P Ciavarra

  Journal of neuroimmunology. 09/2010; 226(1-2):81-92.

  Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair V... [more] Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS.
• 3.04

  Impact points

  Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system.

  Christina D Steel, Suzanne M Hahto, Richard P Ciavarra

  Virology. 04/2009;

  Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective a... [more] Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45(high)CD11b(+)) and CD8(+) T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8(+) T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-gamma) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.
• 0.39

  Impact points

  Comparison of the lateral tail vein and the retro-orbital venous sinus as routes of intravenous drug delivery in a transgenic mouse model.

  Christina D Steel, Amber L. Stephens, Suzanne M Hahto, Sylvia J Singletary, Richard P Ciavarra

  Lab animal. 02/2008; 37(1):26-32.

  In mice, intravenous injections are commonly administered in the lateral tail vein. This technique is sometimes difficult to carry out and may cause stress to mice. Though injection through the retro-orbital venous sinus can provide certain advantages over lateral tail vein injection, this method is... [more] In mice, intravenous injections are commonly administered in the lateral tail vein. This technique is sometimes difficult to carry out and may cause stress to mice. Though injection through the retro-orbital venous sinus can provide certain advantages over lateral tail vein injection, this method is poorly defined and infrequently used. To compare the efficacy of these two routes of drug delivery, the authors injected MAFIA transgenic mice with the depletion agent AP20187, which selectively induces apoptosis in macrophages. Each mouse received five consecutive daily injections through either the lateral tail vein or the retro-orbital venous sinus. The authors then compared macrophage depletion in different tissues (lung, spleen, bone marrow and peritoneal exudate cells). Both routes of injection were similarly effective. A separate experiment using BALB/c mice indicated that retro-orbital venous sinus injection was the less stressful of the two methods.
• 5.65

  Impact points

  Evaluation of immunological paradigms in a virus model: are dendritic cells critical for antiviral immunity and viral clearance?

  Richard P Ciavarra, Amber Stephens, Sandra Nagy, Margaret Sekellick, Christina Steel

  Journal of immunology (Baltimore, Md. : 1950). 08/2006; 177(1):492-500.

  We have examined the role of dendritic cells (DCs) in the antiviral immune response and viral clearance using a transgenic mouse model (CD11c-diphtheria toxin (DT) receptor GFP) that allows for their conditional ablation in vivo. DT administration systemically ablated conventional and IFN-producing ... [more] We have examined the role of dendritic cells (DCs) in the antiviral immune response and viral clearance using a transgenic mouse model (CD11c-diphtheria toxin (DT) receptor GFP) that allows for their conditional ablation in vivo. DT administration systemically ablated conventional and IFN-producing plasmacytoid DCs (pDCs) in transgenic, but not nontransgenic littermates, without elimination of splenic macrophages. Unexpectedly, early (12 and 48 h postinfection) viral clearance of vesicular stomatitis virus was normal in DC-depleted mice despite markedly reduced serum titers of type I IFN. DC-depleted mice remained virus-free with the exception of a subset (approximately 30%) that developed overwhelming and fatal brain infections 6 days postinfection. However, DT treatment profoundly inhibited clonal expansion of naive CD8+ vesicular stomatitis virus-specific T cells without altering the primary Th1 and Th2 cytokine response. Optimal clonal expansion required pDCs because selective elimination of these cells in vivo with a depleting Ab also suppressed expansion of tetramer+ cells, although Th1/Th2 cytokine production remained unaltered. Collectively, these data indicate that conventional DCs and to a lesser extent pDCs are critical for proliferation of naive antiviral T cells. However, other components of the primary adaptive immune response (Th1/Th2 cytokines) are essentially normal in the absence of DCs, which may account for the efficient viral clearance seen in DC-depleted mice. Thus, sufficient redundancy exists in the immune system to sustain efficient viral clearance despite loss of an APC considered essential for induction of a primary antiviral immune response.
• 3.04

  Impact points

  Impact of macrophage and dendritic cell subset elimination on antiviral immunity, viral clearance and production of type 1 interferon.

  Richard P Ciavarra, Lisa Taylor, Amy R Greene, Nazita Yousefieh, Dale Horeth, Nico van Rooijen, Christina Steel, Betsy Gregory, Mark Birkenbach, Margaret Sekellick

  Virology. 12/2005; 342(2):177-89.

  We report herein that vesicular stomatitis virus (VSV) induced a concurrent primary Th1 (T helper 1) and Th2 cytokine response detectable ex vivo. Liposome-encapsulated clodronate-mediated elimination of CD8- marginal dendritic cells (DCs) and splenic macrophages (m Phi), but not CD8+ interdigitatin... [more] We report herein that vesicular stomatitis virus (VSV) induced a concurrent primary Th1 (T helper 1) and Th2 cytokine response detectable ex vivo. Liposome-encapsulated clodronate-mediated elimination of CD8- marginal dendritic cells (DCs) and splenic macrophages (m Phi), but not CD8+ interdigitating DCs, prior to infection resulted in a markedly diminished chemokine and Th1 (IL-2, interferon-gamma) cytokine response, although the Th2 response (IL-4) remained relatively intact. Repopulation with marginal DCs and marginal metallophilic macrophages (MMM) restored Th1 cytokine profiles but did not restore chemokine responsiveness or reduce VSV-induced morbidity/mortality. Chemokine competency returned approximately 4 weeks post-depletion, which correlated temporally with repopulation of the spleen with marginal zone macrophages (MZM) and red pulp macrophages (RPM). Unexpectedly, virus-induced morbidity persisted for over 1 month post-depletion and was associated with virus dissemination and distinctive histological lesions in the liver. Depletion of interferon-producing plasmacytoid dendritic cells did not account for virus-induced morbidity because serum levels of type I interferon were not diminished in Cl2MBP-liposome-treated mice. Thus, distinct m Phi subsets are critical for chemokine production and viral clearance, and, in their absence, VSV disseminates even in the presence of high titers of interferon.
• 3.23

  Impact points

  Single live cell imaging of chromosomes in chloramphenicol-induced filamentous Pseudomonas aeruginosa.

  Christina Steel, Qian Wan, Xiao-Hong Nancy Xu

  Biochemistry. 02/2004; 43(1):175-82.

  Pseudomonas aeruginosa is a leading opportunistic pathogen in human infections, and it is renowned for its intrinsic resistance to structurally and functionally unrelated antibiotics. Filamentation induced by antibiotics appears to trigger bacteria to depart from a normal growth phase and enter a st... [more] Pseudomonas aeruginosa is a leading opportunistic pathogen in human infections, and it is renowned for its intrinsic resistance to structurally and functionally unrelated antibiotics. Filamentation induced by antibiotics appears to trigger bacteria to depart from a normal growth phase and enter a stationary growth phase. As antibiotic concentrations decline below a therapeutic range, filamentous bacteria begin to divide normally, leading to a more rapid regrowth of the bacteria. Furthermore, filamentous bacteria are associated with an increase in endotoxin release. Moreover, the immune system of a patient needs to cope with uncharacteristic filamentous bacteria. Thus, it is biologically and clinically significant to study and understand bacterial filamentation. In this study, we investigate the frequencies, conditions, and characteristics of a filamentous P. aeruginosa at single cell and single chromosome resolutions. Our results show that filamentous cells (elongated rods) contain multiple copies of the cell's chromosome. It appears that the unsuccessful segregation of replicated chromosomes in an individual cell accompanies the formation of undivided filamentous cells. The quantity of chromosomes and the length of the filamentous wild-type cells increase as the chloramphenicol concentration increases to 50 and 250 microg/mL, suggesting that chloramphenicol induces the filamentation. Filamentation in three strains of P. aeruginosa depends on the expression level of efflux pump (MexAB-OprM) and the minimum inhibitory concentration of chloramphenicol. This study also opens up the new possibility of real-time monitoring of modes of actions of antibiotics in live cells with both temporal and spatial resolution.