Macrophage Microbicidal Activity is Enhanced by Stressor-Exposure
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2012
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu13249607582021-08-03T06:04:18Z Macrophage Microbicidal Activity is Enhanced by Stressor-Exposure Allen, Rebecca G. Biomedical Research Immunology Stress macrophage bacterial killing gut microbiota peroxynitrite <p>Exposure to social stressors is known to prime the innate immune system for enhanced reactivity to inflammatory stimuli, but the mechanisms by which stressor exposure can enhance immune activity are not well-defined. In mice, exposure to a social stressor called social disruption (SDR) increases circulating cytokines and primes splenic macrophages for an enhanced capacity to kill Escherichia coli, primarily through an increased production of the highly microbicidal compound peroxynitrite. Previous results demonstrate that the intestinal microbiota are in part responsible for the SDR-induced increase in circulating cytokines; reducing the microbiota through the use of a broad spectrum antibiotic cocktail prevented the SDR-induced increase in IL-6 and MCP-1. These studies tested the hypothesis that intestinal microbiota also contribute to the stressor-induced increase in the ability of splenic macrophages to kill <i>E.coli</i>. To test this hypothesis with SDR, groups of co-housed male mice were repeatedly defeated through direct interactions between the resident mice and an aggressive intruder. Following stress, <i>E. coli</i> were co-cultured with the splenic macrophages, and the number of bacteria within the macrophages was enumerated at 20 and 90 min (to determine the number of bacteria phagocytosed and then killed, respectively). We also measured changes in iNOS and pro-inflammatory cytokine expression as well as production of both superoxide anion and its reaction product with nitric oxide, peroxynitrite.</p> <p>When endogenous bacterial populations were eliminated through the use of germ free mice or reduced in mice treated with an antibiotic cocktail were stressed with SDR, we failed to observe the characteristic increases in pro-inflammatory cytokine and iNOS expression, superoxide anion, and peroxynitrite production. This lack of stressor-induced changes in splenic macrophage activity was associated with the failure of the stressor to enhance bacterial killing typically associated with SDR. However, when germ free mice were conventionalized to contain the normal gut microbiota and exposed to SDR, the enhanced pro-inflammatory cytokine and iNOS expression, superoxide anion, peroxynitrite, and ultimately the enhanced killing were restored. Additionally, the ability of the gut microbiota to prime splenic macrophages is associated with stressor-increased translocation of bacteria and their products from the intestinal lumen, as evidenced by an increase in circulating peptidoglycan. Importantly, the enhanced translocation of bacterial products is linked with stressor-induced mast cell degranulation and disruption of the intestinal epithelial barrier. When mast cells were inhibited from degranulating in vivo, stressor-exposure failed to enhance splenic macrophage microbicidal activity.</p> <p>Overall, these results indicate that the stressor-enhanced activity of CD11b+ splenic macrophages requires the degranulation of mast cells to disrupt the intestinal barrier and allow the translocation of bacteria and their products. These products stimulate production of pro-inflammatory cytokines which primes the macrophages for enhanced microbicidal activity through increased peroxynitrite production. </p> 2012-01-06 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1324960758 http://rave.ohiolink.edu/etdc/view?acc_num=osu1324960758 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biomedical Research Immunology Stress macrophage bacterial killing gut microbiota peroxynitrite |
| spellingShingle |
Biomedical Research Immunology Stress macrophage bacterial killing gut microbiota peroxynitrite Allen, Rebecca G. Macrophage Microbicidal Activity is Enhanced by Stressor-Exposure |
| author |
Allen, Rebecca G. |
| author_facet |
Allen, Rebecca G. |
| author_sort |
Allen, Rebecca G. |
| title |
Macrophage Microbicidal Activity is Enhanced by Stressor-Exposure |
| title_short |
Macrophage Microbicidal Activity is Enhanced by Stressor-Exposure |
| title_full |
Macrophage Microbicidal Activity is Enhanced by Stressor-Exposure |
| title_fullStr |
Macrophage Microbicidal Activity is Enhanced by Stressor-Exposure |
| title_full_unstemmed |
Macrophage Microbicidal Activity is Enhanced by Stressor-Exposure |
| title_sort |
macrophage microbicidal activity is enhanced by stressor-exposure |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2012 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1324960758 |
| work_keys_str_mv |
AT allenrebeccag macrophagemicrobicidalactivityisenhancedbystressorexposure |
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