Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Front Immunol. 2023 Mar 3;14:1044703. doi: 10.3389/fimmu.2023.1044703. eCollection 2023.
(Mtb) is the primary cause of human tuberculosis (TB) and is currently the second most common cause of death due to a singleinfectious agent. The first line of defense against airborne pathogens, including Mtb, is the respiratory epithelium. One of the innate defenses used by respiratory epithelial cells to prevent microbial infection is an oxidative antimicrobial system consisting of the proteins, lactoperoxidase (LPO) and Dual oxidase 1 (Duox1), the thiocyanate anion (SCN-) and hydrogen peroxide (H2O2), which together lead to the generation of antimicrobial hypothiocyanite (OSCN-) in the airway lumen. OSCN- kills bacteria and viruses in vitro, but the role of this Duox1-based system in bacterial infections in vivo remains largely unknown. The goal of this study was to assess whether Duox1 contributes to the immune response against the unique respiratory pathogen, Mtb.
Duox1-deficient (Duox1 KO) and wild-type (WT) mice were infected with Mtb aerosols and bacterial titers, lung pathology, cytokines and immune cell recruitment were assessed.
Mtb titers in the lung, spleen and liver were not different 30 days after infection between WT and Duox1 KO mice. Duox1 did not affect lung histology assessed at days 0, 30, and 90 post-Mtb infection. Mtb-infected Duox1 KO animals exhibited enhanced production of certain cytokines and chemokines in the airway; however, this response was not associated with significantly higher numbers of macrophages or neutrophils in the lung. B cell numbers were lower, while apoptosis was higher in the pulmonary lesions of Mtb-infected Duox1 KO mice compared to infected WT animals. Taken together, these data demonstrate that while Duox1 might influence leukocyte recruitment to inflammatory cell aggregates, Duox1 is dispensable for the overall clinical course of Mtb lung infection in a mouse model.
（Mtb）是人类结核病（TB）的主要病因，目前是由单一感染因子引起的第二大常见死亡原因。呼吸道上皮细胞是抵御包括 Mtb 在内的空气传播病原体的第一道防线。呼吸道上皮细胞用来防止微生物感染的先天防御之一是由蛋白质、乳过氧化物酶（LPO）和双氧化酶 1（Duox1）、硫氰酸盐阴离子（SCN-）和过氧化氢（H2O2）组成的氧化抗菌系统，它们共同导致气道腔中抗菌次碘酸盐（OSCN-）的产生。OSCN-在体外杀死细菌和病毒，但该 Duox1 为基础的系统在体内细菌感染中的作用在很大程度上仍不清楚。本研究的目的是评估 Duox1 是否有助于对独特的呼吸道病原体 Mtb 的免疫反应。
用 Mtb 气溶胶感染 Duox1 缺陷（Duox1 KO）和野生型（WT）小鼠，并评估细菌滴度、肺部病理、细胞因子和免疫细胞募集情况。
感染 Mtb 30 天后，WT 和 Duox1 KO 小鼠的肺部、脾脏和肝脏中的 Mtb 滴度没有差异。Duox1 不影响 Mtb 感染后 0、30 和 90 天的肺部组织学。与感染 WT 动物的 Mtb 感染 Duox1 KO 动物在气道中产生某些细胞因子和趋化因子的产量增加；然而，这种反应与肺部中巨噬细胞或中性粒细胞的数量没有显著增加相关。与感染 WT 动物的 Mtb 感染 Duox1 KO 动物的肺部病变中的 B 细胞数量较低，而细胞凋亡较高。综上所述，这些数据表明，虽然 Duox1 可能影响白细胞募集到炎症细胞聚集物，但在小鼠模型中，Duox1 对于 Mtb 肺部感染的整体临床过程是可有可无的。
