Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection.
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da Silva Andrea Marques Vieira, Machado Thiago Lazari, Nascimento Ryann de Souza, Rodrigues Miguel Pires Medeiros Diniz, Coelho Felipe Soares, Tubarão Luciana Neves, da Rosa Lorenna Carvalho, Bayma Camilla, Rocha Vanessa Pimenta, Frederico Ana Beatriz Teixeira, Silva Jane, Cunha Danielle Regina de Almeida de Brito E, de Souza Alessandro Fonseca, de Souza Raphaela Barbosa Gonçalves, Barros Caroline Augusto, Fiscina Danielle da Silva, Ribeiro Luiz Claudio Pereira, de Carvalho Carlos Alberto Marques, da Silva Bruno Jorge Duque, Muller Rodrigo, Azamor Tamiris, Melgaço Juliana Gil, Gonçalves Rafael Braga, Ano Bom Ana Paula Dinis
Аннотация
METHODS: We investigated the influence of bovine Lf (bLf) in the immune response during SARS-CoV-2 infection in vitro and in vivo assays.
RESULTS: Our results show a strong binding between bLf and TLR4/NF-κB in silico, as well as an increase in mRNA expression of these genes in peripheral blood mononuclear cells (PBMCs) treated with bLf. Furthermore, the treatment increased TLR4/TLR9 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 IL1B and IL6 in the lung tissue. Furthermore, bLf treatment was able to restore FTH1 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.