Lactoferrin and Its Digestive Fragments Boost Antiviral Immune Responses by Activating Dendritic Cells | Research

The takeaway

Bovine lactoferrin and its digested peptides amplified interferon-alpha production and activated key antiviral immune cells, but only when viral RNA was present.

Digestive fragments equally active
Lactoferrin's pepsin hydrolysate and lactoferricin fragment boosted IFN-α production comparably to intact lactoferrin, suggesting oral consumption preserves immune benefits

What the researchers found

Bovine lactoferrin (LF) and its digestive peptides — including pepsin hydrolysate (LFH) and lactoferricin (LFcin) — significantly increased interferon-alpha (IFN-α) production from human immune cells when viral single-stranded RNA was present. Without viral RNA, lactoferrin had no effect on IFN-α levels, indicating it acts as an immune amplifier rather than a standalone activator.

Lactoferrin also upregulated expression of HLA-DR and CD86 on plasmacytoid dendritic cells (pDCs), markers of immune cell activation. The digestive peptide LFH and the antimicrobial fragment LFcin showed comparable activity, suggesting that lactoferrin retains its immune-boosting properties even after being broken down by stomach enzymes.

Why it matters

Lactoferrin is a naturally occurring protein in milk and other body fluids that has long been studied for antimicrobial and immune-modulating properties. This study provides a specific mechanism for how lactoferrin and its digestive fragments enhance antiviral immunity — by activating plasmacytoid dendritic cells, which are critical first responders to viral infections. The fact that digested fragments retain activity is particularly important because it suggests orally consumed lactoferrin could provide immune benefits.

The numbers in context

LF, LFH, and LFcin all significantly increased IFN-α · LFH and LFcin effects were comparable · HLA-DR and CD86 upregulated on pDCs · Effect only present with ssRNA stimulation

How the study worked

Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult donors and incubated with bovine lactoferrin, its pepsin hydrolysate (LFH), or lactoferricin (LFcin) in the presence or absence of single-stranded RNA derived from HIV. IFN-α concentrations were measured by ELISA, and expression of IFN-α, HLA-DR, and CD86 on plasmacytoid dendritic cells was quantified by flow cytometry.

Who was studied

PBMCs from healthy adult blood donors (ex vivo)

What this study cannot tell us

This is an ex vivo study using isolated human blood cells in a laboratory setting — results may not directly predict what happens when lactoferrin is consumed orally and passes through the full digestive and circulatory systems. The number of blood donors was not specified in the abstract. Only one type of viral stimulus (HIV-derived ssRNA) was tested, so generalizability to other viral infections is uncertain.

How to read the evidence

This is a preliminary ex vivo study using isolated human immune cells. While the results demonstrate a clear mechanism, they have not been confirmed in live human subjects through oral supplementation studies. The evidence is preliminary but mechanistically informative.

When this study was published

Published in 2023, this study adds to the growing body of research on lactoferrin's immune-modulating properties and provides a specific mechanism relevant to antiviral immunity.

The bigger picture

Lactoferrin is one of the most extensively studied bioactive peptide sources, available as a dietary supplement and found naturally in breast milk, saliva, and tears. Understanding exactly how it enhances immune function — through pDC activation and IFN-α amplification — adds mechanistic depth to the growing body of evidence supporting its role in innate immunity. This work is particularly relevant in the context of viral pandemic preparedness, where safe, accessible immune-supporting compounds could serve as adjuncts to vaccines and antivirals.

Questions still open

Does oral lactoferrin supplementation in humans lead to measurable increases in IFN-α production during viral infections?
Would lactoferrin show similar immune-amplifying effects with other viral stimuli beyond HIV-derived ssRNA?
Could lactoferrin peptides be developed as therapeutic immune adjuvants for antiviral treatments?

Common questions

What is lactoferrin and where does it come from?

Lactoferrin is a protein naturally found in milk (especially breast milk), saliva, tears, and other body fluids. Bovine (cow) lactoferrin is widely available as a dietary supplement. When digested, it breaks down into smaller peptides like lactoferricin that retain biological activity.

Does this mean lactoferrin can fight viruses?

This study shows lactoferrin can amplify the body's own antiviral response — specifically, it boosts interferon-alpha production when viral RNA is detected by immune cells. It doesn't directly kill viruses but may help the immune system respond more effectively. However, these results are from laboratory experiments, not from clinical trials in people fighting infections.

Read the original research

Lactoferrin and its digestive peptides induce interferon-α production and activate plasmacytoid dendritic cells ex vivo.

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 36(3), 563-573

View on PubMed ↗Publisher’s paper ↗

Citation

Kubo, Shutaro; Miyakawa, Momoko; Tada, Asuka; Oda, Hirotsugu; Motobayashi, Hideki; Iwabuchi, Sadahiro; Tamura, Shinobu; Tanaka, Miyuki; Hashimoto, Shinichi. (2023). Lactoferrin and its digestive peptides induce interferon-α production and activate plasmacytoid dendritic cells ex vivo.. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 36(3), 563-573. https://doi.org/10.1007/s10534-022-00436-y