Browsing by Author "Walline, Crystal C."

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    Early activation of peripheral monocytes with hallmarks of M1 and M2 monocytic cells in excessive alcohol drinkers: a pilot study
    (BMJ, 2018-06) Walline, Crystal C.; Blum, Janice S.; Linton, Tobyn; Mangiacarne, Darrin; Liangpunsakul, Suthat; Microbiology and Immunology, School of Medicine
    Excessive drinking can lead to the development of immune dysfunction. Our aim is to investigate the effect of alcohol on immune activation from circulating peripheral blood monocytes in excessive drinkers (EDs). Twenty-two EDs and healthy controls were enrolled. Time line follow-back was used to quantify the amount of alcohol consumed in the past 30 days before enrollment. Peripheral blood-derived CD14+ monocytes were isolated for gene expression analyses. Serum interleukin (IL)-6, IL-10 and lipopolysaccharides (LPS) were also measured. We found that serum LPS concentrations were significantly higher in EDs compared with controls (P<0.05). While no differences in the levels of circulating IL-6 and IL-10 were observed, the relative levels of gene transcripts (RQ) for Il6 (an M1-polarizing cytokine) and Il10 (an M2-polarizing cytokine) were significantly higher in peripheral blood-derived monocytes from EDs compared with controls (Il6: P<0.01. Il10: P<0.05). EDs exhibit early immune activation of peripheral blood monocyte mRNA transcripts, notably Il6 and Il10 Future studies are needed to explore the clinical implications of our findings and determine whether the levels of Il6 and Il10 mRNA expression can be used to identify those with excessive drinking and to monitor for alcohol abstinence.
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    Virus-encoded ectopic CD74 enhances poxvirus vaccine efficacy
    (Wiley Blackwell (Blackwell Publishing), 2014-04) Walline, Crystal C.; Deffit, Sarah N.; Wang, Nan; Guindon, Lynette M.; Crotzer, Victoria L.; Liu, Jianyun; Hollister, Kristin; Eisenlohr, Laurence C.; Brutkiewicz, Randy R.; Kaplan, Mark H.; Blum, Janice S.; Department of Microbiology & Immunology, IU School of Medicine
    Vaccinia virus (VV) has been used globally as a vaccine to eradicate smallpox. Widespread use of this viral vaccine has been tempered in recent years because of its immuno-evasive properties, with restrictions prohibiting VV inoculation of individuals with immune deficiencies or atopic skin diseases. VV infection is known to perturb several pathways for immune recognition including MHC class II (MHCII) and CD1d-restricted antigen presentation. MHCII and CD1d molecules associate with a conserved intracellular chaperone, CD74, also known as invariant chain. Upon VV infection, cellular CD74 levels are significantly reduced in antigen-presenting cells, consistent with the observed destabilization of MHCII molecules. In the current study, the ability of sustained CD74 expression to overcome VV-induced suppression of antigen presentation was investigated. Viral inhibition of MHCII antigen presentation could be partially ameliorated by ectopic expression of CD74 or by infection of cells with a recombinant VV encoding murine CD74 (mCD74-VV). In contrast, virus-induced disruptions in CD1d-mediated antigen presentation persisted even with sustained CD74 expression. Mice immunized with the recombinant mCD74-VV displayed greater protection during VV challenge and more robust anti-VV antibody responses. Together, these observations suggest that recombinant VV vaccines encoding CD74 may be useful tools to improve CD4⁺ T-cell responses to viral and tumour antigens.