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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1456634

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

Provisionally accepted
Andréa M. Silva Andréa M. Silva 1*Thiago L. Machado Thiago L. Machado 1Ryann Nascimento Ryann Nascimento 1Miguel P. Rodrigues1 Miguel P. Rodrigues1 1Felipe Coelho Felipe Coelho 1Luciana N. Tubarão Luciana N. Tubarão 1Lorenna Carvalho Da Rosa Lorenna Carvalho Da Rosa 1Camilla Bayma Camilla Bayma 1Vanessa P. Rocha Vanessa P. Rocha 1Ana Beatriz T. Frederico Ana Beatriz T. Frederico 1Jane Silva Jane Silva 1Danielle Regina d. Cunha Danielle Regina d. Cunha 1Alessandro F. Souza Alessandro F. Souza 1Raphaela B. Souza Raphaela B. Souza 2Caroline A. Barros Caroline A. Barros 2Danielle d. Fiscina Danielle d. Fiscina 2Luiz Ribeiro Luiz Ribeiro 3Carlos Alberto M. Carvalho Carlos Alberto M. Carvalho 4Bruno Silva Bruno Silva 1Rodrigo Muller Rodrigo Muller 1Tamiris Azamor Tamiris Azamor 1Juliana G. Melgaço Juliana G. Melgaço 1Rafael B. Gonçalves Rafael B. Gonçalves 2Ana Paula D. Ano Bom Ana Paula D. Ano Bom 1
  • 1 1Instituto de Tecnologia em Imunobiológicos, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
  • 2 Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
  • 3 Hospital Universitário Gaffrée e Guinle, Rio de Janeiro, Rio de Janeiro, Brazil
  • 4 Universidade do Estado do Pará, Belem, Para, Brazil

The final, formatted version of the article will be published soon.

    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. We investigated the influence of bovine lactoferrin (bLf) in the immune response during SARS-CoV-2 infection in vitro, and in vivo assays. Our results show a strong binding between bLf and TLR4/NF-kB in silico, as well as an increase in mRNA expression of these genes in peripheral blood mononuclear cells (PBMC) treated with bLf. Furthermore, the treatment increased TLR4/TLR9 mRNA expression in infected K18-hACE2 mice 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 PBMC 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 proinflammatory markers (GM-CSF/IL-1b/IL-2), and upregulated mRNA expression of IL1B and IL6 in the lung tissue. Furthermore, bLf treatment was able to restore FTH1 levels in brain tissue. The data indicates that bLf can be part of a therapeutic strategy to promote the immunomodulation effect, leading to homeostasis during COVID-19.

    Keywords: Bovine lactoferrin, COVID-19, Immunomodulation, Cytokines, TLR4

    Received: 28 Jun 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Silva, Machado, Nascimento, Rodrigues1, Coelho, Tubarão, Carvalho Da Rosa, Bayma, Rocha, Frederico, Silva, Cunha, Souza, Souza, Barros, Fiscina, Ribeiro, Carvalho, Silva, Muller, Azamor, Melgaço, Gonçalves and Ano Bom. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Andréa M. Silva, 1Instituto de Tecnologia em Imunobiológicos, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.