Impact of diet-induced obesity on the immune system of mice after combined blunt muscle and thorax trauma revealed by high-resolution phenotyping

Obesity as a state of chronic inflammation has been shown to alter and influence the immune response. Due to the increasing prevalence of obesity, it is crucial to understand the ongoing alterations and modifications of the immune system to provide better care options for obese patients. The study presented in this thesis elucidated the implication of DIO on the immune response after a combined muscle and thorax trauma in vivo mainly utilizing regular flow cytometry and the novel mass cytometry. Mechanistically, an effect of DIO that could be revealed during this study is an attenuated splenic response to stimulation through the vagus nerve as part of the inflammatory reflex, likely contributing to the observed prolonged initial inflammation phase in obese mice. This is suggested by data demonstrating a reduction of ChAT+ CD4+ T cells in the spleen of obese mice accompanied by a reduced responsiveness to nicotine treatment after lipopolysaccharide stimulation, which should result in a diminished TNF-α production of splenic macrophages. Generally, a prolonged inflammation phase could be described in obese mice which is characterized by enhanced numbers of circulating neutrophils as well as increased percentages of pro-inflammatory CCR2varCX3CR1+CD62L+Ly6Chi monocytes in obese mice. Furthermore, increased cytokine levels are detectable in the periphery of obese mice, further promoting a pro-inflammatory environment and contributing to an enhanced pro-inflammatory response to the combined trauma. These described changes in the periphery, especially the shifts to inflammation in the monocyte compartment, influence immune cell migration to the inflamed tissues. These changes result in an impairment of the switch of pro-inflammatory M1 to regenerative M2 macrophages in the lung of obese mice. Besides phenotyping immune cells, non-immune cells were analyzed in the muscle showing a lacking expansion of highly proliferative, fibrogenic Sca-1hiCD90- fibro/adipogenic progenitors as a response to the trauma in obese mice, ...