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Effects of CHO-expressed recombinant lactoferrins on mouse dendritic cell presentation and function
Shen-An Hwang1, Marian L Kruzel2, Jeffrey K Actor3
1Department of Pathology, University of Texas-Houston Medical School, Houston, TX, USA.
Innate Immunity
|December 25, 2014
Summary
Recombinant lactoferrin (LF) enhances the Bacillus Calmette-Guérin (BCG) vaccine. Both mouse and human LF modulate immune responses in dendritic cells, with human LF showing promise in heterologous vaccine enhancement.
Area of Science:
- Immunology
- Vaccinology
- Biochemistry
Background:
- Lactoferrin (LF), an iron-binding protein, is known to boost the efficacy of the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine.
- Understanding the immune modulatory effects of recombinant LF is crucial for optimizing vaccine strategies.
Purpose of the Study:
- To investigate the immune modulatory effects of Chinese hamster ovary (CHO) cell-expressed recombinant mouse and human lactoferrins (LF) on mouse bone marrow-derived dendritic cells (BMDCs).
- To compare the homologous and heterologous functions of mouse and human LF in modulating immune responses.
- To assess the potential of human LF in a heterologous system for enhancing BCG vaccine efficacy against Mycobacterium tuberculosis.
Main Methods:
- BCG-infected BMDCs were cultured with either mouse or human recombinant LF.
- Class II presentation molecule expression on BMDCs was examined.
- Cytokine production (IL-12p40, IL-1β, IL-10) by BMDCs was measured.
- Naïve CD4 and CD8 T-cells were overlaid onto treated BMDCs to assess cytokine production (IFN-γ, IL-17).
Main Results:
- Culturing BCG-infected BMDCs with either mouse or human LF decreased the population expressing class II presentation molecules.
- Mouse LF significantly increased IL-12p40, IL-1β, and IL-10 production; human LF increased IL-1β and IL-10.
- Co-culture with mouse LF-treated BMDCs enhanced IFN-γ production by CD4 T-cells, while human LF enhanced IFN-γ and IL-17.
- Co-culture with mouse LF-treated BMDCs increased IFN-γ and IL-17 production by CD8 T-cells; human LF increased only IL-17.
Conclusions:
- This study provides the first parallel examination of mouse and human recombinant LFs on murine dendritic cell function.
- Both mouse and human LF exhibit immunomodulatory effects on BMDCs, influencing cytokine profiles and T-cell responses.
- Human LF demonstrates efficacy in a heterologous system, suggesting its potential for enhancing BCG vaccine effectiveness against Mycobacterium tuberculosis.
