Multi-scale optical imaging of the delayed type hypersensitivity reaction attenuated by rapamycin
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Published on: August 27, 2019
Meijie Luo1, Zhihong Zhang1, Hui Li1
11. Bitton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology (WNLO-HUST), Wuhan 430074, China; ; 2. MoE Key Laboratory for Biomedical Photonics, Department of Biomedical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China;
Abstract:
Neutrophils and monocytes/macrophages (MMs) play important roles in the development of cell-mediated delayed type hypersensitivity (DTH). However, the dynamics of neutrophils and MMs during the DTH reaction and how the immunosuppressant rapamycin modulates their behavior in vivo are rarely reported. Here, we take advantage of multi-scale optical imaging techniques and a footpad DTH reaction model to non-invasively investigate the dynamic behavior and properties of immune cells from the whole field of the footpad to the cellular level. During the classic elicitation phase of the DTH reaction, both neutrophils and MMs obviously accumulated at inflammatory foci at 24 h post-challenge. Rapamycin treatment resulted in advanced neutrophil recruitment and vascular hyperpermeability at an early stage (4 h), the reduced accumulation of neutrophils (> 50% inhibition ratio) at 48 h, and the delayed involvement of MMs in inflammatory foci. The motility parameters of immune cells in the rapamycin-treated reaction at 4 h post-challenge displayed similar mean velocities, arrest durations, mean displacements, and confinements as the classic DTH reaction at 24 h. These results indicate that rapamycin treatment shortened the initial preparation stage of the DTH reaction and attenuated its intensity, which may be due to the involvement of T helper type 2 cells or regulatory T cells.
Insights
Rapamycin alters immune cell dynamics in delayed type hypersensitivity (DTH) reactions. It initially enhances neutrophil recruitment but later reduces neutrophil and delays monocyte/macrophage accumulation, potentially by affecting T helper cells.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Neutrophils and monocytes/macrophages (MMs) are key in delayed type hypersensitivity (DTH).
- In vivo dynamics of these cells and rapamycin's modulation during DTH are poorly understood.
Purpose of the Study:
- To investigate immune cell dynamics during DTH using multi-scale optical imaging.
- To determine how rapamycin affects neutrophil and MM behavior in vivo during DTH.
Main Methods:
- Utilized a footpad DTH reaction model in vivo.
- Employed multi-scale optical imaging to observe immune cell behavior from macro to cellular levels.
- Analyzed immune cell motility parameters including velocity, arrest duration, displacement, and confinement.
Main Results:
- Neutrophils and MMs accumulated at inflammatory sites at 24 hours post-challenge in classic DTH.
- Rapamycin advanced neutrophil recruitment and vascular hyperpermeability at 4 hours.
- Rapamycin reduced neutrophil accumulation by over 50% at 48 hours and delayed MM involvement.
Conclusions:
- Rapamycin treatment shortens the DTH reaction's initial phase and attenuates its intensity.
- Rapamycin's effects may involve T helper type 2 or regulatory T cells.
- Immune cell dynamics are significantly modulated by rapamycin during DTH.
