系统性炎症抑制局部感染时淋巴组织重构和 B 细胞免疫。

Systemic Inflammation Suppresses Lymphoid Tissue Remodeling and B Cell Immunity during Concomitant Local Infection.

机构信息

Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.

Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Melbourne, VIC 3000, Australia.

出版信息

Cell Rep. 2020 Dec 29;33(13):108567. doi: 10.1016/j.celrep.2020.108567.

DOI:10.1016/j.celrep.2020.108567

PMID:33378682

Abstract

Concurrent infection with multiple pathogens occurs frequently in individuals and can result in exacerbated infections and altered immunity. However, the impact of such coinfections on immune responses remains poorly understood. Here, we reveal that systemic infection results in an inflammation-induced suppression of local immunity. During localized infection or vaccination in barrier tissues including the skin or respiratory tract, concurrent systemic infection induces a type I interferon-dependent lymphopenia that impairs lymphocyte recruitment to the draining lymph node (dLN) and induces sequestration of lymphocytes in non-draining LN. This contributes to suppressed fibroblastic reticular cell and endothelial cell expansion and dLN remodeling and impairs induction of B cell responses and antibody production. Our data suggest that contemporaneous systemic inflammation constrains the induction of regional immunity.

摘要

同时感染多种病原体在个体中经常发生，并可能导致感染加重和免疫改变。然而，这种合并感染对免疫反应的影响仍知之甚少。在这里，我们揭示了全身性感染会导致炎症诱导的局部免疫抑制。在包括皮肤或呼吸道在内的屏障组织中发生局部感染或接种疫苗时，同时发生的全身性感染会诱导 I 型干扰素依赖性淋巴细胞减少症，从而损害淋巴细胞向引流淋巴结（dLN）的募集，并导致非引流淋巴结中淋巴细胞的隔离。这导致成纤维网状细胞和内皮细胞的扩张以及 dLN 的重塑受到抑制，并损害了 B 细胞反应和抗体产生的诱导。我们的数据表明，同时发生的全身炎症限制了区域性免疫的诱导。