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Front Immunol
. 2024 Oct 17:15:1456634.
doi: 10.3389/fimmu.2024.1456634. eCollection 2024. Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection
Andrea Marques Vieira da Silva # 1 , Thiago Lazari Machado # 1 , Ryann de Souza Nascimento 1 , Miguel Pires Medeiros Diniz Rodrigues 1 , Felipe Soares Coelho 1 , Luciana Neves Tubarão 1 , Lorenna Carvalho da Rosa 1 , Camilla Bayma 1 , Vanessa Pimenta Rocha 1 , Ana Beatriz Teixeira Frederico 1 , Jane Silva 1 , Danielle Regina de Almeida de Brito E Cunha 1 , Alessandro Fonseca de Souza 1 , Raphaela Barbosa Gonçalves de Souza 2 , Caroline Augusto Barros 2 , Danielle da Silva Fiscina 2 , Luiz Claudio Pereira Ribeiro 3 , Carlos Alberto Marques de Carvalho 4 , Bruno Jorge Duque da Silva 1 , Rodrigo Muller 1 , Tamiris Azamor 1 , Juliana Gil Melgaço 1 , Rafael Braga Gonçalves 2 , Ana Paula Dinis Ano Bom 1
Affiliations
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 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.
Keywords: COVID-19; TLR4; bovine lactoferrin; cytokines; immunomodulation.
. 2024 Oct 17:15:1456634.
doi: 10.3389/fimmu.2024.1456634. eCollection 2024. Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection
Andrea Marques Vieira da Silva # 1 , Thiago Lazari Machado # 1 , Ryann de Souza Nascimento 1 , Miguel Pires Medeiros Diniz Rodrigues 1 , Felipe Soares Coelho 1 , Luciana Neves Tubarão 1 , Lorenna Carvalho da Rosa 1 , Camilla Bayma 1 , Vanessa Pimenta Rocha 1 , Ana Beatriz Teixeira Frederico 1 , Jane Silva 1 , Danielle Regina de Almeida de Brito E Cunha 1 , Alessandro Fonseca de Souza 1 , Raphaela Barbosa Gonçalves de Souza 2 , Caroline Augusto Barros 2 , Danielle da Silva Fiscina 2 , Luiz Claudio Pereira Ribeiro 3 , Carlos Alberto Marques de Carvalho 4 , Bruno Jorge Duque da Silva 1 , Rodrigo Muller 1 , Tamiris Azamor 1 , Juliana Gil Melgaço 1 , Rafael Braga Gonçalves 2 , Ana Paula Dinis Ano Bom 1
Affiliations
- PMID: 39483459
- PMCID: PMC11524939
- DOI: 10.3389/fimmu.2024.1456634
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 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.
Keywords: COVID-19; TLR4; bovine lactoferrin; cytokines; immunomodulation.