Valley Fever Center for Excellence, University of Arizona, Tucson, AZ, United States.
Department of Immunobiology, University of Arizona, Tucson, AZ, United States.
Front Cell Infect Microbiol. 2022 Jan 31;11:796114. doi: 10.3389/fcimb.2021.796114. eCollection 2021.
Tumor necrosis factor alpha (TNFα) is a pluripotent cytokine that is important in many infections, though its role in infection remains poorly understood. The need to understand TNFα in infection has increased recently with the widespread use of TNFα inhibitors for a wide variety of autoimmune conditions. Here, we couple the newly developed infection model using strain Cp1038 and C57BL/6 × DBA/2J F1 (B6D2F1) mice. B6D2F1 mice develop long-lasting control of Cp1038. Treatment of B6D2F1 mice with anti-TNFα antibodies permits significant fungal proliferation and death. Additionally, we show that antibody treatment limited to the first 2 weeks of infection was sufficient to induce this same loss of fungal control. Importantly, anti-TNFα antibody treatment initiated after fungal control leads to a loss of host control. These results highlight the importance of TNFα in both the initial control of murine and ongoing suppression of the fungal disease.
肿瘤坏死因子-α(TNFα)是一种多功能细胞因子,在许多感染中都很重要,但它在感染中的作用仍知之甚少。随着 TNFα 抑制剂在治疗各种自身免疫性疾病中的广泛应用,人们对感染中 TNFα 的理解的需求也日益增加。在这里,我们结合了使用菌株 Cp1038 和 C57BL/6×DBA/2J F1(B6D2F1)小鼠的新开发的感染模型。B6D2F1 小鼠对 Cp1038 具有持久的控制。用抗 TNFα 抗体治疗 B6D2F1 小鼠可导致真菌大量增殖和死亡。此外,我们还表明,仅在感染的前 2 周内进行抗体治疗就足以诱导这种丧失对真菌的控制。重要的是,在宿主控制之后开始的抗 TNFα 抗体治疗会导致宿主控制的丧失。这些结果强调了 TNFα 在控制初始感染和抑制真菌病方面的重要性。