Lipoteichoic Acid from Heyndrickxia coagulans HOM5301 Modulates the Immune Response of RAW 264.7 Macrophages
Open accessAbstract
Heyndrickxia coagulans (formerly Bacillus coagulans) has been increasingly utilized as an immunomodulatory probiotics. Oral administration of H. coagulans HOM5301 significantly boosted both innate and adaptive immunity in mice, particularly by increasing the phagocytic capacity of monocytes/macrophages. Lipoteichoic acid (LTA), a major microbe-associated molecular pattern (MAMP) in Gram-positive bacteria, exhibits differential immunomodulatory effects due to its structural heterogeneity. We extracted, purified, and characterized LTA from H. coagulans HOM5301. The results showed that HOM5301 LTA consists of a glycerophosphate backbone. Its molecular weight is in the range of 10–16 kDa. HOM5301 LTA induced greater productions of nitric oxide, TNFα, and IL-6 in RAW 264.7 macrophages compared to Staphylococcus aureus LTA. Comparative transcriptome and proteome analyses identified the differentially expressed genes and proteins triggered by HOM5301 LTA. KEGG analyses revealed that HOM5301 LTA transcriptionally and translationally activated macrophages through two immune-related pathways: cytokine–cytokine receptor interaction and phagosome formation. Protein–protein interaction network analysis indicated that the pro-inflammatory response elicited by HOM5301 LTA was TLR2-dependent, possibly requiring the coreceptor CD14, and is mediated via the MAPK and NF-kappaB pathways. Our results demonstrate that LTA is an important MAMP of H. coagulans HOM5301 that boosts immune responses, suggesting that HOM5301 LTA may be a promising immunoadjuvant.
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These functions support survival in the infant gut.
“Specifically, 25 unique COGs are implicated in the import and processing of human milk sugars [84] , while others are associated with host-immune interactions [85] and osmotic and pH regulation [86] , i.e., functions that support survival in the infant gut [23,87,88] .”
From Genome-scale insights into the metabolic landscape and evolutionary development of Bifidobacterium bifidum (2026) · cites this paper as [87]
The Introduction and Discussion describe immune interactions, and the Results examine responses of RAW 264.7 macrophages to lipoteichoic acid. Our copy does not connect those functions to survival in the infant gut; searches for infant-gut survival, human milk sugars, and osmotic or pH regulation found no supporting passage. (LLM, conf=0.75)
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
fastp: an ultra-fast all-in-one FASTQ preprocessor
(2018) · doi:10.1093/bioinformatics/bty560 · Cited by 29,721 · see citing works
HISAT: a fast spliced aligner with low memory requirements
Kim, D., Langmead, B., & Salzberg, S. L. (2015) · Nature Methods · doi:10.1038/nmeth.3317 · Cited by 24,112 · see citing works
Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown
Pertea, M., Kim, D., Pertea, G. M., Leek, J. T., & Salzberg, S. L. (2016) · Nature Protocols · doi:10.1038/nprot.2016.095 · Cited by 6,708 · see citing works
Majorbio Cloud: A one‐stop, comprehensive bioinformatic platform for multiomics analyses
Ren, Y., Guo, Y. L., Shi, C., Liu, L., Guo, Q., Han, C., Zhang, D., Zhang, L. J., Liu, B., Gao, H., et al. (2022) · iMeta · doi:10.1002/imt2.12 · Cited by 919 · see citing works
Self-citationTrained immunity — basic concepts and contributions to immunopathology
Ochando, J., Mulder, W. J. M., Madsen, J. C., Netea, M. G., & Duivenvoorden, R. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00633-5 · Cited by 474 · see citing works
Grangette, C., Nutten, S., Palumbo, E., Morath, S., Hermann, C., Dewulf, J., Pot, B., Härtung, T., Pascal Hols, A., & Mercenier, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504084102 · Cited by 443 · see citing works
Modulation of Gut Microbiota and Immune System by Probiotics, Pre-biotics, and Post-biotics
Liu, Y., Wang, J., & Wu, C. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2021.634897 · Cited by 393 · see citing works
Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids
Ryu, Y. H., Baik, J. E., Yang, J. S., Kang, S., Im, J., Yun, C., Kim, D. W., Lee, K., Chung, D. K., Ju, H. R., et al. (2008) · International Immunopharmacology · doi:10.1016/j.intimp.2008.10.014 · Cited by 189 · see citing works
Majeed, M. A., Nagabhushanam, K., Arumugam, S., Majeed, S., & Ali, F. H. M. (2018) · Food & Nutrition Research · doi:10.29219/fnr.v62.1218 · Cited by 184 · see citing works
Impact of intracellular innate immune receptors on immunometabolism
Chou, W.-C., Rampanelli, E., Li, X., & Ting, J. P. ‐. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00780-y · Cited by 170 · see citing works
Nilsen, N. J., Deininger, S., Nonstad, U., Skjeldal, F. M., Husebye, H., Rodionov, D., von Aulock, S., Härtung, T., Lien, E., Bakke, O., et al. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0907656 · Cited by 161 · see citing works
Lipoteichoic Acids, Phosphate-Containing Polymers in the Envelope of Gram-Positive Bacteria
Schneewind, O., & Missiakas, D. M. (2014) · Journal of Bacteriology · doi:10.1128/jb.01155-13 · Cited by 152 · see citing works
Liu, Y., Liu, W., Li, J., Tang, S., Wang, M., Huang, W., Yao, W., & Gao, X. (2018) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2018.10.041 · Cited by 139 · see citing works
GanedenBC30™ cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro
Jensen, G. S., Benson, K. F., Carter, S. G., & Endres, J. R. (2010) · BMC Immunology · doi:10.1186/1471-2172-11-15 · Cited by 137 · see citing works
Kang, S., Sim, J., Yun, C., & Han, S. H. (2016) · Archives of Pharmacal Research · doi:10.1007/s12272-016-0804-y · Cited by 127 · see citing works
Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG
Claes, I. J. J., Segers, M. E., Verhoeven, T. L. A., Dusselier, M., Sels, B. F., Keersmaecker, S. C. J. D., Vanderleyden, J., & Lebeer, S. (2012) · Microbial Cell Factories · doi:10.1186/1475-2859-11-161 · Cited by 116 · see citing works
Balaguer, F., Enrique, M., Llopis, S., Barrena, M., Navarro, V., Álvarez, B., Chenoll, E., Ramón, D., Tortajada, M., & Martorell, P. (2021) · Microbial Biotechnology · doi:10.1111/1751-7915.13769 · Cited by 103 · see citing works
Pyclik, M. J., Šrůtková, D., Schwarzer, M., & Górska, S. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.12.227 · Cited by 92 · see citing works
Structure/function relationships of lipoteichoic acids
Morath, S., von Aulock, S., & Härtung, T. (2005) · Journal of Endotoxin Research · doi:10.1177/09680519050110061001 · Cited by 85 · see citing works
Multi-spectrometric analyses of lipoteichoic acids isolated from Lactobacillus plantarum
Jang, K., Baik, J. E., Han, S. H., Chung, D. K., & Kim, B. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.03.107 · Cited by 75 · see citing works
Structure and Anti-Inflammation Potential of Lipoteichoic Acids Isolated from Lactobacillus Strains
Lü, Q., Guo, Y., Yang, G., Cui, L., Wu, Z. F., Zeng, X., Pan, D., & Cai, Z. (2022) · Foods · doi:10.3390/foods11111610 · Cited by 65 · see citing works
Visualization of proteomics data using R and Bioconductor
Gatto, L., Breckels, L. M., Naake, T., & Gibb, S. (2015) · PROTEOMICS · doi:10.1002/pmic.201400392 · Cited by 59 · see citing works
Phagosome as the Organelle Linking Innate and Adaptive Immunity
Kagan, J. C., & Iwasaki, A. (2012) · Traffic · doi:10.1111/j.1600-0854.2012.01377.x · Cited by 58 · see citing works
Probiotics and Trained Immunity
Cortes‐Perez, N. G., de LeBlanc, A. D. M., Gómez-Gutiérrez, J. G., LeBlanc, J. G., & Bermúdez‐Humarán, L. G. (2021) · Biomolecules · doi:10.3390/biom11101402 · Cited by 50 · see citing works
Liang, J., Li, C., Chen, Z., Guo, F., Dou, J., Wang, T., & Xu, Z. S. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1415790 · Cited by 47 · see citing works
Self-citationAnaya‐Loyola, M. A., Enciso‐Moreno, J. A., López-Ramos, J. E., García-Marín, G., Álvarez, M. Y. O., Vega-García, A. M., Mosqueda, J., García-Gutiérrez, D. G., Keller, D., & Pérez‐Ramírez, I. F. (2019) · Food Research International · doi:10.1016/j.foodres.2019.108567 · Cited by 42 · see citing works
Hoffman, J. R., Hoffman, M. W., Zelicha, H., Gepner, Y., Willoughby, D. S., Feinstein, U., & Ostfeld, I. (2019) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003265 · Cited by 35 · see citing works
Friedrich, A. D., Leoni, J., Paz, M. L., & Maglio, D. H. G. (2022) · Nutrients · doi:10.3390/nu14030723 · Cited by 34 · see citing works
Wang, Y., Lin, J., Cheng, Z., Wang, T., Chen, J., & Long, M. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5463290 · Cited by 33 · see citing works
Self-citationRole of Lipoteichoic Acid from the Genus Apilactobacillus in Inducing a Strong IgA Response
Matsuzaki, C., Shiraishi, T., Chiou, T., Nakashima, Y., Higashimura, Y., Yokota, S., Yamamoto, K., & Takahashi, T. (2022) · Applied and Environmental Microbiology · doi:10.1128/aem.00190-22 · Cited by 32 · see citing works
Han, J., Zhao, X., Zhao, X., Li, P., & Gu, Q. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.126825 · Cited by 30 · see citing works
Self-citationKim, Y., Park, J. Y., Kim, H., et al. (2020) · Microbial Pathogenesis · doi:10.1016/j.micpath.2020.104360 · Cited by 22 · see citing works
Wu, S., Liu, H., Li, S., Sun, H., He, X., Huang, Y., & Long, H. (2021) · Marine Drugs · doi:10.3390/md19040217 · Cited by 18 · see citing works
Kim, W., Yu, H., Lee, N., & Paik, H. (2022) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-022-09949-x · Cited by 13 · see citing works
Efficacy of Cisplatin–CXCR4 Antagonist Combination Therapy in Oral Cancer
Yoshida, S., Kawai, H., Soe, Y., et al. (2024) · Cancers · doi:10.3390/cancers16132326 · Cited by 11 · see citing works
Zhang, S., Zhang, D., Wang, T., Lee, S., Lim, C., Zhao, Y., & Li, P. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105694 · Cited by 8 · see citing works
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- Authors
- Zhang, S., Li, P., Zhang, X., Ding, Y., Wang, T., Lee, S., Xu, Y., Lim, C., & Shang, N.
- Affiliations
- China Agricultural University (CN)
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing 101312, China
- Corresponding author
- Shang, Nan
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2024-09-06
- Volume
- 16
- Issue
- 17
- Pages
- 3014
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC11396992
- OpenAlex
- W4402314921
- Cited by
- 13
- References
- 37
- Citations by year
- 2026: 8 · 2025: 5
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (32201994, RD06)
- Coree Beijing Co., Ltd (32201994, RD06)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant-Microbe Interactions and Immunity
- Keywords
- lipoteichoic acid, Heyndrickxia coagulans, Bacillus coagulans, probiotics, immunomodulation, macrophages, RAW 264.7 macrophages, TLR2, CD14, nitric oxide, TNF-α, interleukin-6, phagosome formation, MAPK signaling, NF-κB signaling, immunoadjuvant
- MeSH terms
- RAW 264.7 Cells, Animals, Bacillus, Lipopolysaccharides, Macrophages, Nitric Oxide, Teichoic Acids, Tumor Necrosis Factor-alpha, Interleukin-6, Probiotics, Toll-Like Receptor 2, Mice
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