Bacterial infections negatively affect public health. Many organisms mobilize lipids as a source of energy to resist against pathogens. One pathway, the BMP pathway, plays a role in the regulation of lipid metabolism. By understanding the use of fat in cases such as loss of appetite in infection could serve as an early indicator of when an infection may occur. Preliminary data done by Ph.D student Katerina at Queens College demonstrate utilization of lipid as a form of resistance against pathogens, which was mobilized at 24 hours. Although innate immunity is the first line of defense against pathogens, the earliest immunity response is unknown. Therefore, the objective within this study is to determine the temporal dynamics of lipid alteration after pathogen exposure. To test this, two genotypes, wildtype (N2) and dbl1 mutant of Caenorhabditis elegans, were exposed to the pathogen Serratia marsescens for defined time points: 18 hours, 19 hours, and 22 hours. Results showed exposure for 18 hours and 22 hours demonstrated no lipid mobilization (p = 0.7289 and p = 0.1879, respectively). Suggesting lipid and innate immunity was not yet mobilized at exposure times less than 22 hours. Further applications by exposing pathogen to day 1 adults and to C. elegans eggs from hatch, could determine whether lipid allocation may have had an impact on the study.

References

• Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Innate Immunity. In Molecular Biology of the Cell. 4th edition. Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK26846/
• Akira, S., Uematsu, S., & Takeuchi, O. (2006). Pathogen Recognition and Innate Immunity. Cell, 124(4), 783–801. https://doi.org/10.1016/j.cell.2006.02.015
• Hubler, M. J., & Kennedy, A. J. (2016). Role of lipids in the metabolism and activation of immune cells. The Journal of Nutritional Biochemistry, 34, 1–7. https://doi.org/10.1016/j.jnutbio.2015.11.002
• Sheehan, G., Garvey, A., Croke, M., & Kavanagh, K. (2018). Innate humoral immune defences in mammals and insects: The same, with differences ? Virulence, 9(1), 1625– 1639. https://doi.org/10.1080/21505594.2018.1526531
• Zheng, Y., Yang, H., Zhang, X., & Gao, C. (2023). Regulation of SARS-CoV-2 infection and antiviral innate immunity by ubiquitination and ubiquitin-like conjugation. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1866(4), 194984. https://doi.org/10.1016/j.bbagrm.2023.194984
• Dantzer, R. (2009). Cytokine, Sickness Behavior, and Depression. Immunology and Allergy Clinics of North America, 29(2), 247–264. https://doi.org/10.1016/j.iac.2009.02.002
• Luo, S., Zhang, X., & Xu, H. (2020). Don’t Overlook Digestive Symptoms in Patients With 2019 Novel Coronavirus Disease (COVID-19). Clinical Gastroenterology and Hepatology, 18(7), 1636–1637. https://doi.org/10.1016/j.cgh.2020.03.043
• Diamond, M. S., & Kanneganti, T.-D. (2022). Innate immunity: The first line of defense against SARS-CoV-2. Nature Immunology, 23(2), Article 2. https://doi.org/10.1038/s41590-021-01091-0
• Doron, S., & Gorbach, S. L. (2008). Bacterial Infections: Overview. International Encyclopedia of Public Health, 273–282. https://doi.org/10.1016/B978-012373960-5.00596-7
• Deshpande, R., Lee, B., Qiao, Y., & Grewal, S. S. (2022). TOR signalling is required for host lipid metabolic remodelling and survival following enteric infection in Drosophila. Disease Models & Mechanisms, 15(5), dmm049551. https://doi.org/10.1242/dmm.049551
• Clark, J. F., Ciccarelli, E. J., Kayastha, P., Ranepura, G., Yamamoto, K. K., Hasan, M. S., Madaan, U., Meléndez, A., & Savage-Dunn, C. (2021). BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans. PLoS Genetics, 17(10), e1009836. https://doi.org/10.1371/journal.pgen.1009836
• Madaan, U., Yzeiraj, E., Meade, M., Clark, J. F., Rushlow, C. A., & Savage-Dunn, C. (2018). BMP Signaling Determines Body Size via Transcriptional Regulation of Collagen Genes in Caenorhabditis elegans. Genetics, 210(4), 1355–1367.
• Ciccarelli, E. J., Bendelstein, M., & Savage-Dunn, C. (2023). BMP signaling to pharyngeal muscle in the C. elegans immune response to bacterial pathogen regulates anti-microbial peptide expression and pharyngeal pumping. bioRxiv: The Preprint Server for Biology, 2023.03.06.531324. https://doi.org/10.1101/2023.03.06.531324
• Medzhitov, R., Schneider, D. S., & Soares, M. P. (2012). Disease Tolerance as a Defense Strategy. Science (New York, N.Y.), 335(6071), 936–941. https://doi.org/10.1126/science.1214935
• Marshall, J. S., Warrington, R., Watson, W., & Kim, H. L. (2018). An introduction to immunology and immunopathology. Allergy, Asthma & Clinical Immunology, 14(2), 49. https://doi.org/10.1186/s13223-018-0278-1
• Wang, R. N., Green, J., Wang, Z., Deng, Y., Qiao, M., Peabody, M., Zhang, Q., Ye, J., Yan, Z., Denduluri, S., Idowu, O., Li, M., Shen, C., Hu, A., Haydon, R. C., Kang, R., Mok, J., Lee, M. J., Luu, H. L., & Shi, L. L. (2014). Bone Morphogenetic Protein (BMP) signaling in development and human diseases. Genes & Diseases, 1(1), 87–105. https://doi.org/10.1016/j.gendis.2014.07.005
• Savage-Dunn, C. (2005). TGF-β signaling. WormBook. https://doi.org/10.1895/wormbook.1.22.1
• Sconocchia, T., & Sconocchia, G. (2021). Regulation of the Immune System in Health and Disease by Members of the Bone Morphogenetic Protein Family. Frontiers in Immunology, 12, 802346. https://doi.org/10.3389/fimmu.2021.802346
• Zhang, H., Schulz, T. J., Espinoza, D. O., Huang, T. L., Emanuelli, B., Kristiansen, K., & Tseng, Y.-H. (2010). Cross Talk between Insulin and Bone Morphogenetic Protein Signaling Systems in Brown Adipogenesis. Molecular and Cellular Biology, 30(17), 4224. https://doi.org/10.1128/MCB.00363-10
• Clark, J. F., Meade, M., Ranepura, G., Hall, D. H., & Savage-Dunn, C. (2018). Caenorhabditis elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling. G3 (Bethesda, Md.), 8(1), 343–351. https://doi.org/10.1534/g3.117.300416
• Mallo, G. V., Kurz, C. L., Couillault, C., Pujol, N., Granjeaud, S., Kohara, Y., & Ewbank, J. J. (2002). Inducible Antibacterial Defense System in C. elegans. Current Biology, 12(14), 1209–1214. https://doi.org/10.1016/S0960-9822(02)00928-4
• Sheehan, G., Garvey, A., Croke, M., & Kavanagh, K. (2018). Innate humoral immune defences in mammals and insects: The same, with differences ? Virulence, 9(1), 1625– 1639. https://doi.org/10.1080/21505594.2018.1526531
• Madaan, U., Faure, L., Chowdhury, A., Ahmed, S., Ciccarelli, E. J., Gumienny, T. L., & Savage-Dunn, C. (2020). Feedback regulation of BMP signaling by Caenorhabditis elegans cuticle collagens. Molecular Biology of the Cell, 31(8), 825–832. https://doi.org/10.1091/mbc.E19-07-0390
• Roberts, A. F., Gumienny, T. L., Gleason, R. J., Wang, H., & Padgett, R. W. (2010). Regulation of genes affecting body size and innate immunity by the DBL-1/BMP-like pathway in Caenorhabditis elegans. BMC Developmental Biology, 10(1), 61. https://doi.org/10.1186/1471-213X-10-61
• Farley, S. E., Kyle, J. E., Leier, H. C., Bramer, L. M., Weinstein, J., Bates, T. A., Lee, J.-Y., Metz, T. O., Schultz, C., & Tafesse, F. G. (2022). A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants. bioRxiv: The Preprint Server for Biology, 2022.02.14.480430. https://doi.org/10.1101/2022.02.14.480430
• Doron, S., & Gorbach, S. L. (2008). Bacterial Infections: Overview. International Encyclopedia of Public Health, 273–282. https://doi.org/10.1016/B978-012373960-5.00596-7
• Stuhr, N. L., Nhan, J. D., Hammerquist, A. M., Van Camp, B., Reoyo, D., & Curran, S. P. (2022). Rapid Lipid Quantification in Caenorhabditis elegans by Oil Red O and Nile Red Staining. Bio-Protocol, 12(5), e4340. https://doi.org/10.21769/BioProtoc.4340
• Wang, A., Huen, S. C., Luan, H. H., Baker, K., Rinder, H., Booth, C. J., & Medzhitov, R. (2018). Glucose metabolism mediates disease tolerance in cerebral malaria. Proceedings of the National Academy of Sciences of the United States of America, 115(43), 11042– 11047. https://doi.org/10.1073/pnas.1806376115
• Rao, S., Schieber, A. M. P., O’Connor, C. P., Leblanc, M., Michel, D., & Ayres, J. S. (2017). Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission. Cell, 168(3), 503-516.e12. https://doi.org/10.1016/j.cell.2017.01.006
• Kurz, C. L., Chauvet, S., Andrès, E., Aurouze, M., Vallet, I., Michel, G. P. F., Uh, M., Celli, J., Filloux, A., De Bentzmann, S., Steinmetz, I., Hoffmann, J. A., Finlay, B. B., Gorvel, J.-P., Ferrandon, D., & Ewbank, J. J. (2003). Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening. The EMBO Journal, 22(7), 1451–1460. https://doi.org/10.1093/emboj/cdg159