title: Effects of CHO-expressed recombinant lactoferrins on mouse dendritic cell presentation and function.
abstract: Lactoferrin (LF), a natural iron-binding protein, has previously demonstrated effectiveness in enhancing the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine. This report investigates immune modulatory effects of Chinese hamster ovary (CHO) cell-expressed recombinant mouse and human LFs on mouse bone marrow-derived dendritic cells (BMDCs), comparing homologous and heterologous functions. BCG-infected BMDCs were cultured with LF, and examined for class II presentation molecule expression. Culturing of BCG-infected BMDCs with either LF decreased the class II molecule-expressing population. Mouse LF significantly increased the production of IL-12p40, IL-1β and IL-10, while human LF-treated BMDCs increased only IL-1β and IL-10. Overlaying naïve CD4 T-cells onto BCG-infected BMDCs cultured with mouse LF increased IFN-γ, whereas the human LF-exposed group increased IFN-γ and IL-17 from CD4 T cells. Overlay of naïve CD8 T cells onto BCG-infected BMDCs treated with mouse LF increased the production of IFN-γ and IL-17, while similar experiments using human LF only increased IL-17. This report is the first to examine mouse and human recombinant LFs in parallel experiments to assess murine DC function. These results detail the efficacy of the human LF counterpart used in a heterologous system to understand LF-mediated events that confer BCG efficacy against Mycobacterium tuberculosis challenge.
authors.affiliation: Department of Pathology, University of Texas-Houston Medical School, Houston, TX, USA.
authors.forename: Shen-An
authors.initials: SA
authors.lastname: Hwang
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas-Houston Medical School, Houston, TX, USA.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Kruzel
authors.affiliation: Department of Pathology, University of Texas-Houston Medical School, Houston, TX, USA Program in Immunology, University of Texas Health Science Center, Houston, TX, USA Jeffrey.K.Actor@uth.tmc.edu.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Actor
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001407:Bacillus; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007781:Lactoferrin / Q000096:biosynthesis*; D051379:Mice; D009169:Mycobacterium tuberculosis; D011994:Recombinant Proteins / Q000096:biosynthesis; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control
chemical_list: D020381:Interleukin-17; D011994:Recombinant Proteins; D007781:Lactoferrin
keywords: BCG; Lactoferrin; adjuvant; dendritic cells