CCR7/dendritic cell axis mediates early bacterial dissemination in Orientia tsutsugamushi-infected mice

• DOI: 10.3389/fimmu.2022.1061031
• Publication Date: 2022-12-22T04:53:19Z
• Authors: Yuejin Liang; Hui Wang; Casey Gonzales; Joseph Thiriot; Piyanate Sunyakum...; Peter C. Melby; Jiaren Sun; Lynn Soong
• Keywords: Orientia tsutsugamushi

Scrub typhus is a life-threatening zoonosis caused by the obligate intracellular bacterium Orientia tsutsugamushi ( Ot ) that transmitted infected larvae of trombiculid mites. However, mechanism which disseminates from bite site to visceral organs remains unclear; host innate immunity against bacterial dissemination and replication during early infection poorly understood. In this study, using an intradermal mouse model fluorescent probe-labeled , we assessed dynamic pattern immune cell responses at inoculation site. We found neutrophils were first responders migrated into skin for uptake. greatly induced neutrophil activation, -neutrophil interaction remarkably promoted death both in vitro vivo . Depletion did not alter mice, as evidenced similar burdens draining lymph nodes (dLN) day 3, well lungs brains 14, compared control mice. Instead, dendritic cells (DCs) macrophages played role Trojan horse dLN. Importantly, absence homing receptor CCR7 or neutralization its ligand, CCL21, significantly impaired DC migration, resulting reduced Taken together, our study sheds light on CCR7/dendritic cell-mediated provides new insights therapeutic vaccine development strategies scrub typhus.