New insights into the skin immune landscape at single-cell resolution during cutaneous infection by an obligate intracellular bacterium

Tick-borne bacteria encounter a complex immune environment in the skin. Yet how different cells respond at the infection site, and how local reactions relate to symptoms elsewhere in the body, remain unclear. Understanding this early encounter could help explain variation in the clinical presentation of rickettsial infections.

Research reported in hLife examines how skin cells respond to Rickettsia heilongjiangensis, a bacterium that grows inside host cells. Monocyte-derived macrophage gene expression differed across interferon receptor backgrounds, while neutrophils showed signatures linked to energy production and protein degradation in both wild-type and interferon receptor-deficient mice. Interferons are immune signaling proteins, and these comparisons show that different skin cells respond differently when interferon receptor signaling is disrupted. Separately, among patients with confirmed spotted fever group rickettsial infection, local skin lesions were associated with less frequent fever.

“We observed distinct response patterns among immune cells in infected skin,” said corresponding author Na Jia, a researcher at the Beijing Institute of Microbiology and Epidemiology, China. “Monocyte-derived macrophages showed different responses across mice with different interferon receptor backgrounds, while recruited neutrophils showed an oxidative stress response in all three mouse models. These findings reveal how distinct immune cells contribute to the skin’s response to Rickettsia heilongjiangensis.”

The team fluorescently labeled the bacterium using bioorthogonal metabolic labeling and click chemistry, introduced it into mouse skin, and sorted cells by fluorescence for single-cell RNA sequencing. This technique records gene expression in individual cells, helping distinguish responses among immune cells and surrounding tissue cells at the infection site. The models comprised wild-type mice, mice lacking the type I interferon receptor gene Ifnar1, and mice lacking both Ifnar1 and the type II interferon receptor gene Ifngr1. Future functional studies could test whether these responses contribute to bacterial control or tissue injury.

The research was conducted by teams at the Beijing Institute of Microbiology and Epidemiology, and Tianjin Medical University, with support from the National Science and Technology Major Project for the Prevention and Control of Emerging and Major Infectious Diseases (2025ZD01901400); the National Natural Science Foundation of China’s Young Scientists Fund (A) (82525059); the National Key Research and Development Program of China (2021YFA1301202); the National Natural Science Foundation of China (82473677, 82273676, 32400963 and 92357305); the Fujian Provincial Foreign Cooperation Project (2024I0034); and the Scientific Research Project of Fuzhou Customs (FK2024-02).

About Author:

Na Jia is a researcher at the Beijing Institute of Microbiology and Epidemiology, China. Her research focuses on the discovery of emerging natural-focal diseases and tracing their origins. She has published more than 100 SCI-indexed papers, including articles in Cell, Nature, and The New England Journal of Medicine. Her research has received the Second Prize of the State Natural Science Award and the First Prize of the Beijing Science and Technology Award. Her work has also been recognized as an outstanding achievement by the National Natural Science Foundation of China, designated as ESI Highly Cited Papers, and awarded three-star recommendations by F1000.

DOI Link:

https://doi.org/10.1016/j.hlife.2026.09.002