Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States.
Front Cell Infect Microbiol. 2021 Feb 19;11:580679. doi: 10.3389/fcimb.2021.580679. eCollection 2021.
Influenza A virus (IAV) is a respiratory pathogen that infects millions of people each year. Both seasonal and pandemic strains of IAV are capable of causing severe respiratory disease with a high risk of respiratory failure and opportunistic secondary infection. A strong inflammatory cytokine response is a hallmark of severe IAV infection. The widespread tissue damage and edema in the lung during severe influenza is largely attributed to an overexuberant production of inflammatory cytokines and cell killing by resident and infiltrating leukocytes. Mast cells (MCs) are a sentinel hematopoietic cell type situated at mucosal sites, including the lung. Poised to react immediately upon detecting infection, MCs produce a vast array of immune modulating molecules, including inflammatory cytokines, chemokines, and proteases. As such, MCs have been implicated as a source of the immunopathology observed in severe influenza. However, a growing body of evidence indicates that MCs play an essential role not only in inducing an inflammatory response but in suppressing inflammation as well. MC-derived immune suppressive cytokines are essential to the resolution of a number of viral infections and other immune insults. Absence of MCs prolongs infection, exacerbates tissue damage, and contributes to dissemination of the pathogen to other tissues. Production of cytokines such as IL-10 and IL-6 by MCs is essential for mitigating the inflammation and tissue damage caused by innate and adaptive immune cells alike. The two opposing functions of MCs-one pro-inflammatory and one anti-inflammatory-distinguish MCs as master regulators of immunity at the site of infection. Amongst the first cells to respond to infection or injury, MCs persist for the duration of the infection, modulating the recruitment, activation, and eventual suppression of other immune cells. In this review, we will discuss the immune modulatory roles of MCs over the course of viral infection and propose that the immune suppressive mediators produced by MCs are vital to minimizing immunopathology during influenza infection.
甲型流感病毒（IAV）是一种呼吸道病原体，每年感染数百万人。季节性和大流行株的 IAV 都能导致严重的呼吸道疾病，有发生呼吸衰竭和机会性继发感染的高风险。强烈的炎症细胞因子反应是严重 IAV 感染的标志。严重流感期间肺部广泛的组织损伤和水肿主要归因于炎症细胞因子的过度产生以及驻留和浸润的白细胞的细胞杀伤。肥大细胞（MC）是位于黏膜部位（包括肺部）的哨兵造血细胞类型。MC 一旦检测到感染，就会立即做出反应，产生大量免疫调节分子，包括炎症细胞因子、趋化因子和蛋白酶。因此，MC 被认为是严重流感中观察到的免疫病理学的来源。然而，越来越多的证据表明，MC 不仅在诱导炎症反应中而且在抑制炎症中都起着至关重要的作用。MC 衍生的免疫抑制性细胞因子对于许多病毒感染和其他免疫损伤的消退是必不可少的。MC 缺失会延长感染、加重组织损伤，并导致病原体向其他组织传播。MC 产生的细胞因子，如 IL-10 和 IL-6，对于减轻先天和适应性免疫细胞引起的炎症和组织损伤是必不可少的。MC 的两种相反功能——一种促炎，一种抗炎——将 MC 区分为感染部位免疫调节的主要调控者。MC 是对感染或损伤做出第一反应的细胞之一，在感染持续期间持续存在，调节其他免疫细胞的募集、激活和最终抑制。在这篇综述中，我们将讨论 MC 在病毒感染过程中的免疫调节作用，并提出 MC 产生的免疫抑制介质对于最大限度减少流感感染中的免疫病理学是至关重要的。
