Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models

Renhua Li; Michael Rouse; Brendon T Pace; Scott F Grey; Kimberly Mclaughlin; Seth A Schobel; Mark P Simons

doi:10.3389/fmicb.2023.1240176

Host CD3⁺ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models

Front Microbiol. 2023 Sep 11:14:1240176. doi: 10.3389/fmicb.2023.1240176. eCollection 2023.

Authors

Renhua Li^{1

2

3}, Michael Rouse^{1

2

3

4}, Brendon T Pace^{1

5}, Scott F Grey^{1

2

3}, Kimberly Mclaughlin^{1

2

3}, Seth A Schobel^{1

2

3}, Mark P Simons^{1

6}

Affiliations

¹ Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
² Surgical Critical Care Initiative (SC2i), Uniformed Services University (USU), Bethesda, MD, United States.
³ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD, United States.
⁴ Walter Reed National Military Medical Center, Bethesda, MD, United States.
⁵ Eastern Virginia Medical School, Norfolk, VA, United States.
⁶ Naval Medical Research Center, Silver Spring, MD, United States.

Abstract

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.

Keywords: CD3+ T-cells; bacterial bioburden; bi-directional relationship between bacterial burden and host immune responses; phage treatment; systems biology; wound healing.