Ravesloot-Chavez Marietta M, Van Dis Erik, Fox Douglas, Anaya-Sanchez Andrea, Espich Scott, Nguyenla Xammy Huu, Rawal Sagar, Samani Helia, Ballinger Mallory, Thomas Henry F, Kotov Dmitri I, Vance Russell E, Nachman Michael W, Stanley Sarah A
Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, United States.
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Elife. 2025 Sep 12;13:RP102441. doi: 10.7554/eLife.102441.
Tuberculosis is a heterogeneous disease in humans with individuals exhibiting a wide range of susceptibility. This heterogeneity is not captured by standard laboratory mouse lines. We used a new collection of 19 wild-derived inbred mouse lines collected from diverse geographic sites to identify novel phenotypes during () infection. Wild-derived mice have heterogeneous immune responses to infection that result in differential ability to control disease at early time points. Correlation analysis with multiple parameters including sex, weight, and cellular immune responses in the lungs revealed that enhanced control of infection is associated with increased numbers of CD4 T cells, CD8 T cells, and B cells. Surprisingly, we did not observe strong correlations between IFN-γ production and control of infection. Although in most lines high neutrophils were associated with susceptibility, we identified a mouse line that harbors high neutrophil numbers yet controls infection. Using single-cell RNA sequencing, we identified a novel neutrophil signature associated with failure to control infection.
结核病在人类中是一种异质性疾病，个体表现出广泛的易感性。标准实验室小鼠品系无法体现这种异质性。我们使用了从不同地理位点收集的19个野生近交小鼠品系的新集合，以识别在（）感染期间的新表型。野生小鼠对感染具有异质性免疫反应，这导致它们在早期阶段控制疾病的能力有所不同。对包括性别、体重和肺部细胞免疫反应在内的多个参数进行的相关性分析表明，对感染的更好控制与CD4 T细胞、CD8 T细胞和B细胞数量的增加有关。令人惊讶的是，我们没有观察到IFN-γ产生与感染控制之间的强相关性。尽管在大多数品系中，高嗜中性粒细胞数量与易感性相关，但我们鉴定出一个嗜中性粒细胞数量高但能控制感染的小鼠品系。通过单细胞RNA测序，我们鉴定出一种与无法控制感染相关的新型嗜中性粒细胞特征。
