Recombinant human lactoferrin induces human and mouse dendritic cell maturation<i>via</i>Toll‐like receptors 2 and 4

Spadaro, Michela; Arigoni, Maddalena; Cantarella, Daniela; Forni, Guido; Pericle, Federica; Pascolo, Steve; Calogero, Raffaele; Cavallo, Federica

doi:10.1096/fj.13-229591

Cited by 31 publications

(18 citation statements)

References 51 publications

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“…This limited data suggest that the CD16 + macrophage may demonstrate changes in LPS induced TLR-4 signaling. Lactoferrin’s mechanism to regulate LPS induced inflammation is thought to occur through the LPS-TLR-4 signaling cascade [59–65]. One potential hypothesis for why recombinant human lactoferrin did not affect CD16 + macrophage cytokine/chemokine production maybe due to the innate changes in the LPS-TLR-4 signaling cascade, compared to CD14 + macrophage response.…”

Section: Discussionmentioning

confidence: 99%

Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS

2016

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Lactoferrin, an iron-binding glycoprotein found in mammalian mucosal secretions and granules of neutrophils, possesses several immune modulatory properties. Published reports indicate that lactoferrin enhances the efficacy of the tuberculosis vaccine, BCG (Bacillus Calmette Guerin), both by increasing macrophage and dendritic cell ability to stimulate receptive T cells and by modulating the inflammatory response. This report is the first to demonstrate the effects of a recombinant human lactoferrin (10 μg/ mL) on human PBMC derived CD14+ and CD16+ macrophages stimulated with a strong (LPS, 10 ng/mL) or weaker (BCG, MOI 1:1) stimulator of inflammation. After 3 days culture, LPS and human lactoferrin treated CD14+ cells significantly increased production of IL-10, IL-6, and MCP-1 compared to the LPS only group. In contrast, similarly treated CD16+ macrophages increased production of IL-12p40 and IL-10 and decreased TNF-α. Limited changes were observed in BCG stimulated CD14+ and CD16+ macrophages with and without lactoferrin. Analysis of surface expression of antigen presentation and co-stimulatory molecules demonstrated that CD14+ macrophages, when stimulated with BCG or LPS and cultured with lactoferrin, increased expression of CD86. CD16+ macrophages treated with lactoferrin showed a similar trend of increase in CD86 expression, but only when stimulated with BCG.

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Section: Discussionmentioning

confidence: 99%

Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS

2016

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“…Epithelial DCs ( 83 ), keratinocytes ( 84 ), and oral epithelial cells ( 85 ) bear CD14 and TLRs able to recognize LTF. More importantly, LTF can trigger maturation of DCs through TLR2 and TLR4 ( 86 ), with such events known to promote DC migration to adjacent lymph nodes ( 87 ). Orally ingested LTF may also interact with intestinal epithelial cells expressing TLRs ( 88 ).…”

Section: Lactoferrin and General Physiologic Homeostasismentioning

confidence: 99%

Lactoferrin in a Context of Inflammation-Induced Pathology

2017

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Much progress has been achieved to elucidate the function of lactoferrin (LTF), an iron-binding glycoprotein, in the milieu of immune functionality. This review represents a unique examination of LTF toward its importance in physiologic homeostasis as related to development of disease-associated pathology. The immunomodulatory nature of this protein derives from its unique ability to “sense” the immune activation status of an organism and act accordingly. Underlying mechanisms are proposed whereby LTF controls disease states, thereby pinpointing regions of entry for LTF in maintenance of various physiological pathways to limit the magnitude of tissue damage. LTF is examined as a first line mediator in immune defense and response to pathogenic and non-pathogenic injury, as well as a molecule critical for control of oxidative cell function. Mechanisms of interaction of LTF with its receptors are examined, with a focus on protective effects via regulation of enzyme activities and reactive oxygen species production, immune deviation, and prevention of cell apoptosis. Indeed, LTF serves as a critical control point in physiologic homeostasis, functioning as a sensor of immunological performance related to pathology. Specific mediation of tissue pathophysiology is described for maintenance of intestinal integrity during endotoxemia, elicited airway inflammation due to allergens, and pulmonary damage during tuberculosis. Finally, the role of LTF to alter differentiation of adaptive immune function is examined, with specific recognition of its utility as a vaccine adjuvant to control subsequent lymphocytic reactivity. Overall, it is clear that while the ability of LTF to both sequester iron and to direct reactive oxygen intermediates is a major factor in lessening damage due to excessive inflammatory responses, further effects are apparent through direct control over development of higher order immune functions that regulate pathology due to insult and injury. This culminates in attenuation of pathological damage during inflammatory injury.

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“…HLf adheres to the DNA structures released due to chromatin decondensation and spreading exerting its antimicrobial properties ( 119 ). In vitro experiments showed that recombinant hLf is able to induce maturation of antigen-presenting cells such as dendritic cells, thus suggesting that it can represent a link in shaping adaptive immunity ( 120 ). Depending on the external stimulus (pathogens, allergen, tumor antigens, etc.)…”

Section: Lactobacilli and Lf Host Immune System Modulationmentioning

confidence: 99%

Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense

et al. 2018

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The innate defense system of the female mucosal genital tract involves a close and complex interaction among the healthy vaginal microbiota, different cells, and various proteins that protect the host from pathogens. Vaginal lactobacilli and lactoferrin represent two essential actors in the vaginal environment. Lactobacilli represent the dominant bacterial species able to prevent facultative and obligate anaerobes outnumber in vaginal microbiota maintaining healthy microbial homeostasis. Several mechanisms underlie the protection exerted by lactobacilli: competition for nutrients and tissue adherence, reduction of the vaginal pH, modulation of immunity, and production of bioactive compounds. Among bioactive factors of cervicovaginal mucosa, lactoferrin, an iron-binding cationic glycoprotein, is a multifunctional glycoprotein with antibacterial, antifungal, antiviral, and antiparasitic activities, recently emerging as an important modulator of inflammation. Lactobacilli and lactoferrin are largely under the influence of female hormones and of paracrine production of various cytokines. Lactoferrin is strongly increased in lower genital tract mucosal fluid of women affected by Neisseria gonorrheae, Chlamydia trachomatis, and Trichomonas vaginalis infections promoting both innate and adaptive immune responses. In vaginal dysbiosis characterized by low amounts of vaginal lactobacilli and increased levels of endogenous anaerobic bacteria, the increase in lactoferrin could act as an immune modulator assuming the role normally played by the healthy microbiota in vaginal mucosa. Then lactoferrin and lactobacilli may be considered as biomarkers of altered microbial homeostasis at vaginal level. Considering the shortage of effective treatments to counteract recurrent and/or antibiotic-resistant bacterial infections, the intravaginal administration of lactobacilli and lactoferrin could be a novel efficient therapeutic strategy and a valuable tool to restore mucosal immune homeostasis.

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Recombinant human lactoferrin induces human and mouse dendritic cell maturationviaToll‐like receptors 2 and 4

Cited by 31 publications

References 51 publications

Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS

Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS

Lactoferrin in a Context of Inflammation-Induced Pathology

Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense

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