Naomi Navuluri: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Vinod Kumar Yata: Department of Molecular Biology, Central University of Andhrapradesh, Ananthapuramu, Andhrapradesh, India.
Sudharshan Reddy Dachani: Department of Pharmacology, College of Pharmacy, Shaqra University, Al-Dawadmi Campus, Al-Daadmi, Saudi Arabia.
Kartik Rachakonda: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Narasaiah Kolliputi: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. nkollipu@usf.edu.
Pattern recognition receptors (PRRs) help protect hosts from pathogens in different ways. They bind to pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), or other homeostatic irregularities caused by these patterns to activate an immune response against a pathogen. Certain PRRs activate inflammasomes, leading to cell death and the formation of PANoptosomes, a key process in PANoptosis. PRRs help protect against pathogens, however an excessive number can cause harm to the body and even death. The mechanisms of how to control the PRRs remain unknown. Sundaram et al. [1] address this gap by investigating pathways that activate PANoptosomes in infection-mimicking conditions. They found that the sensor NLRP12 activated PANoptosomes causes inflammation in response to infections leading to the hypothesis that targeting the sensor NLRP12 could be a means to stop the harmful effects of excessive PRRs.This discovery suggests that targeting NLRP12 could mitigate the harmful effects of PRR overactivation, offering a potential therapeutic avenue.
Sundaram, B., Pandian, N., Mall, R., Wang, Y., Sarkar, R., Kim, H. J., Malireddi, R., Karki, R., Janke, L. J., Vogel, P., & Kanneganti, T. D. (2023). NLRP12-panoptosome activates panoptosis and pathology in response to heme and PAMPs. Cell, 186, 2783���2801. https://doi.org/10.1016/j.cell.2023.05.005 .
[DOI: 10.1016/j.cell.2023.05.005]
Sharma, B. R., Karki, R., Rajesh, Y., & Kanneganti, T. D. (2023). Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis). Journal of Biological Chemistry, 299(9), 105141.
[DOI: 10.1016/j.jbc.2023.105141]
Christgen, S., Zheng, M., Kesavardhana, S., Karki, R., Malireddi, R., Banoth, B., Place, D. E., Briard, B., Sharma, B. R., Tuladhar, S., Samir, P., Burton, A., & Kanneganti, T. D. (2020). Identification of the PANoptosome: A molecular platform triggering pyroptosis, apoptosis, and necroptosis (PANoptosis). Frontiers in Cellular and Infection Microbiology, 10, 237.
[DOI: 10.3389/fcimb.2020.00237]
Choudhury, S. M., Sarkar, R., Karki, R., & Kanneganti, T. D. (2024). A comparative study of apoptosis, pyroptosis, necroptosis, and PANoptosis components in mouse and human cells. PLoS One, 19(2), e0299577.
[DOI: 10.1371/journal.pone.0299577]
Karki, R., Sundaram, B., Sharma, B. R., Lee, S., Malireddi, R., Nguyen, L. N., Christgen, S., Zheng, M., Wang, Y., Samir, P., Neale, G., Vogel, P., & Kanneganti, T. D. (2021). ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell Reports, 37(3), 109858.
[DOI: 10.1016/j.celrep.2021.109858]
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016). Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature, 535(7610), 153���158.
[DOI: 10.1038/nature18629]
Malireddi, R. S., Sharma, B. R., Bynigeri, R. R., Wang, Y., Lu, J., & Kanneganti, T. D. (2023). ZBP1 drives IAV-induced NLRP3 inflammasome activation and lytic cell death, PANoptosis, independent of the necroptosis executioner MLKL. Viruses, 15(11), 2141.
[DOI: 10.3390/v15112141]
Sundaram, B., Pandian, N., Kim, H. J., Abdelaal, H. M., Mall, R., Indari, O., Sarkar, R., Tweedell, R. E., Alonzo, E. Q., Klein, J., Pruett-Miller, S. M., Vogel, P., & Kanneganti, T. D. (2024). NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation. Cell, 187, 4061���4077.
[DOI: 10.1016/j.cell.2024.05.034]
Wang, C., Yang, T., Xiao, J., Xu, C., Alippe, Y., Sun, K., Kanneganti, T.-D., Monahan, J. B., Abu-Amer, Y., Lieberman, J. & Mbalaviele, G. (2021). Activation of GSDME compensates for GSDMD deficiency in a mouse model of NLRP3 inflammasomopathy. BioRxiv, 2021���01. https://doi.org/10.1101/2021.01.06.425634 .
Neogi, U., Elaldi, N., Appelberg, S., Ambikan, A., Kennedy, E., Dowall, S., Bagci, B. K., Gupta, S., Rodriguez, J. E., Svensson-Akusj��rvi, S., Monteil, V., Vegvari, A., Benfeitas, R., Banerjea, A., Weber, F., Hewson, R., & Mirazimi, A. (2022). Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo hemorrhagic fever viruses for novel therapeutic target. eLife, 11, e76071.
[DOI: 10.7554/eLife.76071]
Connor, J. H., Yen, J., Caballero, I. S., Garamszegi, S., Malhotra, S., Lin, K., Hensley, L., & Goff, A. J. (2015). Transcriptional profiling of the immune response to Marburg virus infection. Journal of Virology, 89(19), 9865���9874.
[DOI: 10.1128/JVI.01142-15]
Zaki, M. H., Vogel, P., Malireddi, R. K., Body-Malapel, M., Anand, P. K., Bertin, J., Green, D. R., Lamkanfi, M., & Kanneganti, T. D. (2011). The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis. Cancer Cell, 20(5), 649���660. https://doi.org/10.1016/j.ccr.2011.10.022 .
[DOI: 10.1016/j.ccr.2011.10.022]
Tsao, Y.-P., Tseng, F.-Y., Chao, C.-W., Chen, M.-H., Yeh, Y.-C., Abdulkareem, B. O., Chen, S. Y., Chuang, W. T., Chang, P. C., Chen, I. C., Wang, P. H., Wu, C. S., Tsai, C. Y., & Chen, S. T. (2023). NLRP12 is an innate immune checkpoint for repressing IFN signatures and attenuating lupus nephritis progression. Journal of Clinical Investigation, 133(9), e157272 https://doi.org/10.1172/jci171350 .
[DOI: 10.1172/jci171350]
Valadares, D. G., Clay, O. S., Chen, Y., Scorza, B. M., Cassel, S. L., Sutterwala, F. S., & Wilson, M. E. (2023). NLRP12-expressing dendritic cells mediate both dissemination of infection and adaptive immune responses in visceral leishmaniasis. iScience, 26(3), 106163 https://doi.org/10.1016/j.isci.2023.106163 .
[DOI: 10.1016/j.isci.2023.106163]
