Gestal Monica C, Blas-Machado Uriel, Johnson Hannah M, Rubin Lily N, Dewan Kalyan K, Bryant Claire, Tiemeyer Michael, Harvill Eric T
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Department of Pathology, Athens Veterinary Diagnostic Laboratory, University of Georgia, Athens, GA 30602, USA.
Microorganisms. 2020 Nov 17;8(11):1808. doi: 10.3390/microorganisms8111808.
Recent findings revealed pivotal roles for eosinophils in protection against parasitic and viral infections, as well as modulation of adaptive immune responses in the gastric mucosa. However, the known effects of eosinophils within the respiratory tract remain predominantly pathological, associated with allergy and asthma. Simulating natural respiratory infections in mice, we examined how efficient and well-adapted pathogens can block eosinophil functions that contribute to the immune response. , a natural pathogen of the mouse, uses the sigma factor to regulate expression of mechanisms that interfere with eosinophil recruitment and function. When is disrupted, immunomodulators are dysregulated, and eosinophils are recruited to the lungs, suggesting they may contribute to much more efficient generation of adaptive immunity induced by this mutant. Eosinophil-deficient mice failed to produce pro-inflammatory cytokines, to recruit lymphocytes, to organize lymphoid aggregates that resemble Bronchus Associated Lymphoid Tissue (BALT), to generate an effective antibody response, and to clear bacterial infection from the respiratory tract. Importantly, the failure of eosinophil-deficient mice to produce these lymphoid aggregates indicates that eosinophils can mediate the generation of an effective lymphoid response in the lungs. These data demonstrate that efficient respiratory pathogens can block eosinophil recruitment, to inhibit the generation of robust adaptive immune responses. They also suggest that some post-infection sequelae involving eosinophils, such as allergy and asthma, might be a consequence of bacterial mechanisms that manipulate their accumulation and/or function within the respiratory tract.
最近的研究结果揭示了嗜酸性粒细胞在抵御寄生虫和病毒感染以及调节胃黏膜适应性免疫反应中的关键作用。然而，嗜酸性粒细胞在呼吸道内的已知作用主要仍是病理性的，与过敏和哮喘相关。通过在小鼠中模拟自然呼吸道感染，我们研究了高效且适应性良好的病原体如何阻断有助于免疫反应的嗜酸性粒细胞功能。小鼠的一种天然病原体利用σ因子来调节干扰嗜酸性粒细胞募集和功能的机制的表达。当该因子被破坏时，免疫调节剂失调，嗜酸性粒细胞被募集到肺部，这表明它们可能有助于由这种突变体诱导产生更有效的适应性免疫。缺乏嗜酸性粒细胞的小鼠无法产生促炎细胞因子、募集淋巴细胞、形成类似于支气管相关淋巴组织（BALT）的淋巴聚集物、产生有效的抗体反应以及清除呼吸道细菌感染。重要的是，缺乏嗜酸性粒细胞的小鼠无法产生这些淋巴聚集物，这表明嗜酸性粒细胞可以介导肺部有效淋巴反应的产生。这些数据表明，高效的呼吸道病原体可以阻断嗜酸性粒细胞的募集，从而抑制强大的适应性免疫反应的产生。它们还表明，一些涉及嗜酸性粒细胞的感染后后遗症，如过敏和哮喘，可能是细菌操纵其在呼吸道内的积聚和/或功能的结果。
