牛乳铁蛋白在 SARS-CoV-2 感染期间的免疫调节作用。

Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection.

机构信息

Departamento de Desenvolvimento Experimental e Pré-Clinico (DEDEP), Instituto de Tecnologia em Imunobiológico, Bio-Manguinhos, Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.

Departamento de Bioquímica, Instituto Biomédico, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Front Immunol. 2024 Oct 17;15:1456634. doi: 10.3389/fimmu.2024.1456634. eCollection 2024.

DOI:10.3389/fimmu.2024.1456634

PMID:39483459

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11524939/

Abstract

INTRODUCTION

Lactoferrin (Lf) is an important immunomodulator in infections caused by different agents. During SARS-CoV-2 infection, Lf can hinder or prevent virus access to the intracellular environment. Severe cases of COVID-19 are related to increased production of cytokines, accompanied by a weak type 1 interferon response.

METHODS

We investigated the influence of bovine Lf (bLf) in the immune response during SARS-CoV-2 infection and assays.

RESULTS

Our results show a strong binding between bLf and TLR4/NF-κB , as well as an increase in mRNA expression of these genes in peripheral blood mononuclear cells (PBMCs) treated with bLf. Furthermore, the treatment increased mRNA expression in infected K18-hACE2 mouse blood, indicating an activation of innate response. Our results show that, when bLf was added, a reduction in the NK cell population was found, presenting a similar effect on PD-1 in TCD4 and TCD8 cells. In the culture supernatant of PBMCs from healthy participants, bLf decreased IL-6 levels and increased CCL5 in COVID-19 participants. In addition, K18-hACE2 mice infected and treated with bLf presented an increase of serum pro-inflammatory markers (GM-CSF/IL-1β/IL-2) and upregulated mRNA expression of and in the lung tissue. Furthermore, bLf treatment was able to restore levels in brain tissue.

DISCUSSION

The data indicate that bLf can be part of a therapeutic strategy to promote the immunomodulation effect, leading to homeostasis during COVID-19.

摘要

简介

乳铁蛋白（Lf）是由不同病原体引起的感染中的一种重要免疫调节剂。在 SARS-CoV-2 感染期间，Lf 可以阻止或防止病毒进入细胞内环境。COVID-19 的严重病例与细胞因子的大量产生有关，同时伴有较弱的 1 型干扰素反应。

方法

我们研究了牛乳铁蛋白（bLf）在 SARS-CoV-2 感染期间对免疫反应的影响，并进行了相关实验。

结果

我们的结果显示，bLf 与 TLR4/NF-κB 之间存在强烈的结合，并且 bLf 处理外周血单核细胞（PBMCs）后这些基因的 mRNA 表达增加。此外，该处理增加了感染 K18-hACE2 小鼠血液中的 mRNA 表达，表明先天反应被激活。我们的结果表明，当添加 bLf 时，NK 细胞群减少，TCD4 和 TCD8 细胞中的 PD-1 也表现出类似的效应。在健康参与者的 PBMC 培养上清液中，bLf 降低了 IL-6 水平，增加了 COVID-19 参与者中的 CCL5。此外，感染并接受 bLf 治疗的 K18-hACE2 小鼠表现出血清促炎标志物（GM-CSF/IL-1β/IL-2）水平升高，肺组织中和基因的 mRNA 表达上调。此外，bLf 治疗能够恢复脑组织中的水平。