Immunotherapy

Introduction

In the ever-evolving field of microbiology and immunology, a groundbreaking study has recently surfaced, shedding light on the potential use of microbial DNA as an immunomodulatory agent. Lactic acid bacteria (LAB), commonly known for their benefits in the food industry and human health, have now been found to play a significant role in stimulating the immune system, specifically the plasmacytoid dendritic cells (pDCs), which are crucial for antiviral responses.

The study, published in BMC Microbiology [DOI: 10.1186/s12866-019-1458-y], significantly contributes to the understanding of the relationship between LAB’s genomic DNA structure and defense activation. It paves the way for innovative approaches to enhance immune response and opens doors to new possibilities in nutritional science, vaccine adjuvants, and therapeutic interventions.

The research, ethically and rigorously conducted in Japan, involved meticulous in vitro screenings of DNA fragments from the genome of Lactococcus lactis strain Plasma (LC-Plasma). The findings, of which full disclosure is published in BMC Microbiology, are not just a testament to technical prowess but also shine a light on the CpG motif’s role – a specific DNA sequence highly regarded for its immune-stimulating capabilities.

The study primarily focused on a particular strain of LAB, LC-Plasma, known for its potent immunoactivity, specifically its ability to stimulate plasmacytoid dendritic cells through the TLR9-Myd88 pathway – a critical mechanism for antiviral defense. The team discovered that fragments containing a higher number of CpG motifs were more efficient in activating pDCs, implying a positive and significant correlation between the CpG motif copy number and the pDCs stimulatory activity (R = 0.491, p < 0.01).

However, the research indicated that the CpG motif copy number was not the sole factor. It introduced an additional perspective, suggesting the percentage of guanine (G) and cytosine (C) – known as the G+C content – in the DNA plays a vital role in pDC activation. The lower the G+C content, the more potent the fragments seemed to be, thus presenting further considerations in the design of DNA-based immune stimulants.

In terms of practical applications, this study potentially revolutionizes the way we approach immune health. The novel method of in silico screening for bacterial species capable of activating pDCs hints at future strategies in developing new probiotics that could prevent or curb infections. Continuous exploration in this arena indicates a promising horizon for advancements in precision health science and personalized medicine.

References

1. Jounai K, Ikado K, Sugimura T, Ano Y, Braun J, Fujiwara D. (2012). “Spherical lactic acid bacteria activate plasmacytoid dendritic cells immunomodulatory function via TLR9-dependent crosstalk with myeloid dendritic cells.” PLoS One.
DOI: 10.1371/journal.pone.0032588

2. Shida K, Sato T, Iizuka R, Hoshi R, Watanabe O, Igarashi T, Miyazaki K, Nanno M, Ishikawa F. (2015). “Daily intake of fermented milk with Lactobacillus casei strain Shirota reduces the incidence and duration of upper respiratory tract infections in healthy middle-aged office workers.” Eur J Nutr.
DOI: 10.1007/s00394-015-1056-1

3. Swiecki M, Colonna M. (2010). “Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance.” Immunol Rev.
DOI: 10.1111/j.0105-2896.2009.00881.x

4. Fujii T, Jounai K, Horie A, Takahashi H, Suzuki H, Ohshio K, Fujiwara D, Yamamoto N. (2017). “Effects of heat-killed Lactococcus lactis subsp. lactis JCM 5805 on mucosal and systemic immune parameters, and antiviral reactions to influenza virus in healthy adults; a randomized controlled double-blind study.” Journal of Functional Foods.
DOI: 10.1016/j.jff.2017.06.011

5. Makino S., Ikegami S., Kano H., Sashihara T., Sugano H., Horiuchi H., Saito T., Oda M. (2006). “Immunomodulatory Effects of Polysaccharides Produced by Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1.” Journal of Dairy Science.
DOI: 10.3168/jds.S0022-0302(06)72560-7

Ethical considerations, including the welfare of animals, were respected, with research methodologies approved by the Committee for Animal Experiment at Kirin Company and adhering to the Guidelines for Proper Conduct of Animal Experiments stipulated by the Science Council of Japan.

Keywords

1. Plasmacytoid dendritic cells
2. Lactic acid bacteria DNA
3. Immunomodulation
4. CpG motifs in immunotherapy
5. Genomic DNA sequencing and immune activation

Conclusion

The pioneering work by Dr. Akira Horie, Dr. Toshio Fujii, and their colleagues is a groundbreaking stride in understanding immune modulation at the DNA level. This compelling breakthrough ensures the scientific community and the public that LAB’s DNA can potentially be tailored to boost the body’s natural defenses. More importantly, it delivers hope for possibly enhancing current health interventions.

Lastly, the scientific community can anticipate that this seminal work will spawn a multitude of research projects, all aiming to harness the full potential of LAB and microbial DNA to strengthen human immunity. As this robust foundation is laid, the future appears promising for the use of LAB DNA in fostering health and combating disease.