tetano
Editor, Senior Moderator
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[SUP] #[/SUP][SUP] 1 [/SUP], Thiago Lazari Machado[SUP] #[/SUP][SUP] 1 [/SUP], Ryann de Souza Nascimento[SUP] 1 [/SUP], Miguel Pires Medeiros Diniz Rodrigues[SUP] 1 [/SUP], Felipe Soares Coelho[SUP] 1 [/SUP], Luciana Neves Tubarão[SUP] 1 [/SUP], Lorenna Carvalho da Rosa[SUP] 1 [/SUP], Camilla Bayma[SUP] 1 [/SUP], Vanessa Pimenta Rocha[SUP] 1 [/SUP], Ana Beatriz Teixeira Frederico[SUP] 1 [/SUP], Jane Silva[SUP] 1 [/SUP], Danielle Regina de Almeida de Brito E Cunha[SUP] 1 [/SUP], Alessandro Fonseca de Souza[SUP] 1 [/SUP], Raphaela Barbosa Gonçalves de Souza[SUP] 2 [/SUP], Caroline Augusto Barros[SUP] 2 [/SUP], Danielle da Silva Fiscina[SUP] 2 [/SUP], Luiz Claudio Pereira Ribeiro[SUP] 3 [/SUP], Carlos Alberto Marques de Carvalho[SUP] 4 [/SUP], Bruno Jorge Duque da Silva[SUP] 1 [/SUP], Rodrigo Muller[SUP] 1 [/SUP], Tamiris Azamor[SUP] 1 [/SUP], Juliana Gil Melgaço[SUP] 1 [/SUP], Rafael Braga Gonçalves[SUP] 2 [/SUP], Ana Paula Dinis Ano Bom[SUP] 1 [/SUP]
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[SUP]+[/SUP] and TCD8[SUP]+[/SUP] 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[SUP] #[/SUP][SUP] 1 [/SUP], Thiago Lazari Machado[SUP] #[/SUP][SUP] 1 [/SUP], Ryann de Souza Nascimento[SUP] 1 [/SUP], Miguel Pires Medeiros Diniz Rodrigues[SUP] 1 [/SUP], Felipe Soares Coelho[SUP] 1 [/SUP], Luciana Neves Tubarão[SUP] 1 [/SUP], Lorenna Carvalho da Rosa[SUP] 1 [/SUP], Camilla Bayma[SUP] 1 [/SUP], Vanessa Pimenta Rocha[SUP] 1 [/SUP], Ana Beatriz Teixeira Frederico[SUP] 1 [/SUP], Jane Silva[SUP] 1 [/SUP], Danielle Regina de Almeida de Brito E Cunha[SUP] 1 [/SUP], Alessandro Fonseca de Souza[SUP] 1 [/SUP], Raphaela Barbosa Gonçalves de Souza[SUP] 2 [/SUP], Caroline Augusto Barros[SUP] 2 [/SUP], Danielle da Silva Fiscina[SUP] 2 [/SUP], Luiz Claudio Pereira Ribeiro[SUP] 3 [/SUP], Carlos Alberto Marques de Carvalho[SUP] 4 [/SUP], Bruno Jorge Duque da Silva[SUP] 1 [/SUP], Rodrigo Muller[SUP] 1 [/SUP], Tamiris Azamor[SUP] 1 [/SUP], Juliana Gil Melgaço[SUP] 1 [/SUP], Rafael Braga Gonçalves[SUP] 2 [/SUP], Ana Paula Dinis Ano Bom[SUP] 1 [/SUP]
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[SUP]+[/SUP] and TCD8[SUP]+[/SUP] 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.