Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA.
Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA
mSphere. 2021 Mar 24;6(2):e00213-21. doi: 10.1128/mSphere.00213-21.
is a devastating opportunistic fungal pathogen. It mostly impacts people in an immunocompromised state, such as people living with HIV/AIDS and following organ transplantation. Macrophages, in addition to being a major cellular reservoir of HIV-1, represent a unique niche in which both and HIV-1 can coinhabit in the course of natural infection. Here, we report the observation that HIV-1 infection of THP-1 macrophages increases the rate at which they phagocytose cells. We investigated the tumor necrosis factor alpha (TNF-α) signaling and nuclear factor kappa B (NF-κB) activation in human monocyte-derived macrophages infected with HIV-1 alone, as well as those coinfected with HIV-1 and Our findings showed that while HIV-1 infection alone upregulates TNF-α production and activates NF-κB signaling, coinfection drastically and rapidly dampens this proinflammatory response. These data suggest an antagonism between two important human pathogens during coinfection of macrophages. Fungal infections are one of the leading causes of death for people who live with HIV/AIDS. Even though these pathogens are independently well studied, it is still enigmatic how coinfection with HIV-1 and alters gene expression and cellular processes, especially in clinically relevant cell types. Understanding the interplay between these two pathogens is especially critical because mortality largely depends on the host's immunocompromised state during viral infection. Studying this coinfection is challenging since HIV-1 only infects human cells, and the modified murine HIV-1 virus does not reproduce the clinical landmarks of HIV-1 infection or AIDS in mice. Our observations shed light on how these two pathogens trigger opposing trends in TNF-α and NF-κB signaling in human monocyte-derived macrophages.
是一种具有破坏性的机会性真菌病原体。它主要影响免疫功能低下的人群，如艾滋病毒/艾滋病患者和器官移植后患者。巨噬细胞不仅是 HIV-1 的主要细胞储库，还是一个独特的小生境，在这个小生境中，和 HIV-1 可以在自然感染过程中共存。在这里，我们报告了观察结果，即 HIV-1 感染 THP-1 巨噬细胞会增加它们吞噬细胞的速度。我们研究了单独感染 HIV-1 的人单核细胞来源巨噬细胞以及同时感染 HIV-1 和的 TNF-α 信号转导和核因子 kappa B (NF-κB) 激活。我们的发现表明，虽然 HIV-1 感染本身会上调 TNF-α 的产生并激活 NF-κB 信号转导，但 共感染会迅速而剧烈地抑制这种促炎反应。这些数据表明，在巨噬细胞共感染时，两种重要的人类病原体之间存在拮抗作用。真菌感染是艾滋病毒/艾滋病患者死亡的主要原因之一。尽管这些病原体已经得到了独立的深入研究，但 HIV-1 与 共感染如何改变基因表达和细胞过程，尤其是在临床相关的细胞类型中，仍然是一个谜。了解这两种病原体之间的相互作用至关重要，因为 的死亡率在很大程度上取决于宿主在病毒感染期间的免疫功能低下状态。研究这种共感染具有挑战性，因为 HIV-1 仅感染人类细胞，而经过修饰的鼠 HIV-1 病毒并不能在小鼠中再现 HIV-1 感染或艾滋病的临床标志。我们的观察结果揭示了这两种病原体如何在人单核细胞来源的巨噬细胞中触发 TNF-α 和 NF-κB 信号转导的相反趋势。
