Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models
Wound healing is a complex system including such key players as host, microbe, and treatments. However, little is known about their dynamic interactions. Here we explored the interplay between: (1) bacterial bioburden and host immune responses, (2) bacterial bioburden and wound size, and (3) treatme...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1240176/full |
| _version_ | 1827820796430516224 |
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| author | Renhua Li Renhua Li Renhua Li Michael Rouse Michael Rouse Michael Rouse Michael Rouse Brendon T. Pace Brendon T. Pace Scott F. Grey Scott F. Grey Scott F. Grey Kimberly Mclaughlin Kimberly Mclaughlin Kimberly Mclaughlin Seth A. Schobel Seth A. Schobel Seth A. Schobel Mark P. Simons Mark P. Simons |
| author_facet | Renhua Li Renhua Li Renhua Li Michael Rouse Michael Rouse Michael Rouse Michael Rouse Brendon T. Pace Brendon T. Pace Scott F. Grey Scott F. Grey Scott F. Grey Kimberly Mclaughlin Kimberly Mclaughlin Kimberly Mclaughlin Seth A. Schobel Seth A. Schobel Seth A. Schobel Mark P. Simons Mark P. Simons |
| author_sort | Renhua Li |
| collection | DOAJ |
| description | Wound healing is a complex system including such key players as host, microbe, and treatments. However, little is known about their dynamic interactions. Here we explored the interplay between: (1) bacterial bioburden and host immune responses, (2) bacterial bioburden and wound size, and (3) treatments and wound size, using murine models and various treatment modalities: Phosphate buffer saline (PBS or vehicle, negative control), doxycycline, and two doses of A. baumannii phage mixtures. We uncovered that the interplay between bacterial bioburden and host immune system may be bidirectional, and that there is an interaction between host CD3+ T-cells and phage dosage, which significantly impacts bacterial bioburden. Furthermore, the bacterial bioburden and wound size association is significantly modulated by the host CD3+ T-cells. When the host CD3+ T-cells (x on log10 scale) are in the appropriate range (1.35 < x < = 1.5), we observed a strong association between colony forming units (CFU) and wound size, indicating a hallmark of wound healing. On the basis of the findings and our previous work, we proposed an integrated parallel systems biology model. |
| first_indexed | 2024-03-12T01:33:12Z |
| format | Article |
| id | doaj.art-6356456d7bfd4043be6bfee51ac2f6e9 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-12T01:33:12Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-6356456d7bfd4043be6bfee51ac2f6e92023-09-11T14:18:42ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-09-011410.3389/fmicb.2023.12401761240176Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse modelsRenhua Li0Renhua Li1Renhua Li2Michael Rouse3Michael Rouse4Michael Rouse5Michael Rouse6Brendon T. Pace7Brendon T. Pace8Scott F. Grey9Scott F. Grey10Scott F. Grey11Kimberly Mclaughlin12Kimberly Mclaughlin13Kimberly Mclaughlin14Seth A. Schobel15Seth A. Schobel16Seth A. Schobel17Mark P. Simons18Mark P. Simons19Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesSurgical Critical Care Initiative (SC2i), Uniformed Services University (USU), Bethesda, MD, United StatesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD, United StatesUniformed Services University of the Health Sciences, Bethesda, MD, United StatesSurgical Critical Care Initiative (SC2i), Uniformed Services University (USU), Bethesda, MD, United StatesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD, United StatesWalter Reed National Military Medical Center, Bethesda, MD, United StatesUniformed Services University of the Health Sciences, Bethesda, MD, United StatesEastern Virginia Medical School, Norfolk, VA, United StatesUniformed Services University of the Health Sciences, Bethesda, MD, United StatesSurgical Critical Care Initiative (SC2i), Uniformed Services University (USU), Bethesda, MD, United StatesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD, United StatesUniformed Services University of the Health Sciences, Bethesda, MD, United StatesSurgical Critical Care Initiative (SC2i), Uniformed Services University (USU), Bethesda, MD, United StatesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD, United StatesUniformed Services University of the Health Sciences, Bethesda, MD, United StatesSurgical Critical Care Initiative (SC2i), Uniformed Services University (USU), Bethesda, MD, United StatesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD, United StatesUniformed Services University of the Health Sciences, Bethesda, MD, United StatesNaval Medical Research Center, Silver Spring, MD, United StatesWound healing is a complex system including such key players as host, microbe, and treatments. However, little is known about their dynamic interactions. Here we explored the interplay between: (1) bacterial bioburden and host immune responses, (2) bacterial bioburden and wound size, and (3) treatments and wound size, using murine models and various treatment modalities: Phosphate buffer saline (PBS or vehicle, negative control), doxycycline, and two doses of A. baumannii phage mixtures. We uncovered that the interplay between bacterial bioburden and host immune system may be bidirectional, and that there is an interaction between host CD3+ T-cells and phage dosage, which significantly impacts bacterial bioburden. Furthermore, the bacterial bioburden and wound size association is significantly modulated by the host CD3+ T-cells. When the host CD3+ T-cells (x on log10 scale) are in the appropriate range (1.35 < x < = 1.5), we observed a strong association between colony forming units (CFU) and wound size, indicating a hallmark of wound healing. On the basis of the findings and our previous work, we proposed an integrated parallel systems biology model.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1240176/fullwound healingphage treatmentbacterial bioburdenCD3+ T-cellssystems biologybi-directional relationship between bacterial burden and host immune responses |
| spellingShingle | Renhua Li Renhua Li Renhua Li Michael Rouse Michael Rouse Michael Rouse Michael Rouse Brendon T. Pace Brendon T. Pace Scott F. Grey Scott F. Grey Scott F. Grey Kimberly Mclaughlin Kimberly Mclaughlin Kimberly Mclaughlin Seth A. Schobel Seth A. Schobel Seth A. Schobel Mark P. Simons Mark P. Simons Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models Frontiers in Microbiology wound healing phage treatment bacterial bioburden CD3+ T-cells systems biology bi-directional relationship between bacterial burden and host immune responses |
| title | Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models |
| title_full | Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models |
| title_fullStr | Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models |
| title_full_unstemmed | Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models |
| title_short | Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models |
| title_sort | host cd3 t cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models |
| topic | wound healing phage treatment bacterial bioburden CD3+ T-cells systems biology bi-directional relationship between bacterial burden and host immune responses |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1240176/full |
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