Bovine Lactoferrin Modulates Mononuclear Cell Activity in Human Palatine Tonsils

TL;DR

Bovine lactoferrin boosts immune response to viruses and reduces inflammation in tonsils, which could help treat colds, tonsillitis, and IgA nephropathy.

Contribution

This study reveals how bovine lactoferrin modulates immune cell activity in tonsils under TLR7 and TLR9 stimulation.

Findings

Bovine LF enhances pDC, T-killer, and B cell activation under TLR7 stimulation without causing inflammation.

Bovine LF suppresses immune cell activation and cytokine production under TLR9 stimulation.

LF reduces BAFF, APRIL, and galactose-deficient IgA1, which are linked to IgA nephropathy.

Abstract

Lactoferrin (LF) is present in tears, nasal secretions, saliva, and milk and maintains mucosal homeostasis. The palatine tonsils represent the first immune tissue to recognize pathogens invading the oral cavity via Toll-like receptors (TLRs). We aimed to investigate the effects of bovine LF on tonsillar immune cells stimulated with ligands of TLR7 or TLR9, which recognize viral single-stranded RNA or bacterial unmethylated CpG DNA. Mononuclear cells isolated from palatine tonsils of patients with recurrent tonsillitis or immunoglobulin A (IgA) nephropathy were cultured with LF, TLR7, or TLR9 ligands. Under TLR7 stimulation, LF enhanced the activation of plasmacytoid dendritic cells (pDCs), T-killer cells, and B cells without inducing inflammatory cytokines. In contrast, under TLR9 stimulation, LF suppressed the activation of pDCs, myeloid dendritic cells, T-helper cells, T-killer cells, B cells, and natural killer cells, as well as the production of TNF-α and IL-6. Moreover, LF decreased the production of the B-cell activation factor (BAFF), a proliferation-inducing ligand (APRIL), and galactose-deficient IgA1, all of which are risk factors of IgA nephropathy. Overall, LF may enhance the immune response against viruses and contribute to immune tolerance against commensal bacteria in the palatine tonsils, indicating potential benefits in managing cold-like symptoms, recurrent tonsillitis, and IgA nephropathy.

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