{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:08:58Z","timestamp":1760148538981,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis is a common disease in sub-Saharan Africa and Asia, where malaria is also prevalent. To determine whether Plasmodium infection might enhance susceptibility to endotoxin shock, we used a mouse model of lipopolysaccharide (LPS) administration. Our results indicated that Plasmodium yoelii infection in mice strongly enhanced the susceptibility of the host to develop endotoxin shock. This increased susceptibility to endotoxin shock was correlated with a synergistic effect of Plasmodium and LPS on the secretion of Tumor Necrosis Factor (TNF). TNF contributed mostly to lethality after the dual challenge since neutralization with an anti-TNF antibody provided protection from death. Plasmodium infection also induced an enhancement of the serum levels of LPS soluble ligands, sCD14 and Lipopolysaccharide Binding Protein. In this regard, our data confirm that Plasmodium infection can profoundly modify responses to secondary bacteria challenges, resulting in dysregulated cytokine expression and pathological effects. If confirmed in humans, LPS soluble receptors might serve as markers of susceptibility to septic shock.<\/jats:p>","DOI":"10.3390\/ijms24108851","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T02:04:05Z","timestamp":1684289045000},"page":"8851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced Mouse Susceptibility to Endotoxin Shock after Plasmodium yoelii Infection Is Correlated with Increased Serum Levels of Lipopolysaccharide Soluble Receptors"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4623-3796","authenticated-orcid":false,"given":"Pyone Pyone","family":"Soe","sequence":"first","affiliation":[{"name":"Unit of Experimental Medicine, de Duve Institute, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"},{"name":"Department of Pathology, University of Medicine 1, Yangon 11131, Myanmar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5681-8915","authenticated-orcid":false,"given":"Jean-Paul","family":"Coutelier","sequence":"additional","affiliation":[{"name":"Unit of Experimental Medicine, de Duve Institute, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2119\/molmed.2010.00001.commentary","article-title":"\u201cMerinoff symposium 2010: Sepsis\u201d-speaking with one voice","volume":"17","author":"Czura","year":"2011","journal-title":"Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1056\/NEJMp1707170","article-title":"Recognizing sepsis as a global health priority\u2014A WHO resolution","volume":"377","author":"Reinhart","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","article-title":"assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations","volume":"193","author":"Fleischmann","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the global burden of disease study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1084\/jem.189.11.1777","article-title":"MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4","volume":"189","author":"Shimazu","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.2402637","article-title":"Structure and function of lipopolysaccharide binding protein","volume":"249","author":"Schumann","year":"1990","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1126\/science.1698311","article-title":"CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein","volume":"249","author":"Wright","year":"1990","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0952-7915(99)80004-1","article-title":"Recognition of gram-negative bacteria and endotoxin by the innate immune system","volume":"11","author":"Ulevitch","year":"1999","journal-title":"Curr. Opin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJM199902113400607","article-title":"Acute-phase proteins and other systemic responses to inflammation","volume":"340","author":"Gabay","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0749-0704(05)70107-X","article-title":"Immunologic response to infection and its role in septic shock","volume":"16","author":"Casey","year":"2000","journal-title":"Crit. Care Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1586\/eri.12.2","article-title":"The immune response to severe bacterial infections: Consequences for therapy","volume":"10","author":"Raftogiannis","year":"2012","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1093\/intimm\/dxm101","article-title":"Divergent roles of IFNs in the sensitization to endotoxin shock by lactate dehydrogenase-elevating virus","volume":"19","author":"Dumoutier","year":"2007","journal-title":"Int. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ataide, M.A., Andrade, W.A., Zamboni, D.S., Wang, D., Souza, M.D.C., Franklin, B.S., Elian, S., Martins, F.S., Pereira, D., and Reed, G. (2014). Malaria-Induced NLRP12\/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003885"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5789","DOI":"10.1073\/pnas.0809742106","article-title":"Malaria primes the innate immune response due to interferon-\u03b3 induced enhancement of toll-like receptor expression and function","volume":"106","author":"Franklin","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"162","DOI":"10.4049\/jimmunol.179.1.162","article-title":"Plasmodium falciparum infection causes proinflammatory priming of human TLR responses","volume":"179","author":"McCall","year":"2007","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Scicluna, B.P., Van \u2019t Veer, C., Nieuwdorp, M., Felsmann, K., and Wlotzka, B. (2013). Role of Tumor Necrosis Factor-a in the human systemic endotoxin-induced transcriptome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079051"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1146\/annurev.iy.13.040195.002253","article-title":"Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin","volume":"13","author":"Ulevitch","year":"1995","journal-title":"Annu. Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1086\/514017","article-title":"Sensitization to lipopolysaccharide in mice with asymptomatic viral infection: Role of T cell-dependent production of interferon-g","volume":"176","author":"Nansen","year":"1997","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.4049\/jimmunol.162.9.5238","article-title":"Synergism for cytokine-mediated disease during concurrent endotoxin and viral challenges: Roles for NK and T cell IFN-g production","volume":"162","author":"Nguyen","year":"1999","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"982","DOI":"10.4049\/jimmunol.166.2.982","article-title":"Viral infection causes rapid sensitization to lipopolysaccharide: Central role of IFN-ab","volume":"166","author":"Nansen","year":"2001","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.4049\/jimmunol.166.4.2658","article-title":"A role for IFN-ab in virus infection-induced sensitization to endotoxin","volume":"166","author":"Doughty","year":"2001","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.4049\/jimmunol.175.3.1498","article-title":"Adenovirus infection dramatically augments lipopolysaccharide-induced TNF production and sensitizes to lethal shock","volume":"175","author":"Szalay","year":"2005","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e03394-19","DOI":"10.1128\/mBio.03394-19","article-title":"A virus hosted in malaria-infected blood protects against T cell-mediated inflammatory diseases by impairing DC function in a Type I IFN-dependent manner","volume":"11","author":"Hassan","year":"2020","journal-title":"mBio"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e0132522","DOI":"10.1128\/mbio.01325-22","article-title":"Intestinal injury biomarkers predict mortality in pediatric severe malaria","volume":"13","author":"Sarangam","year":"2022","journal-title":"mBio"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1002\/eji.202048936","article-title":"Novel antibodies that selctively block mouse IL-12 enable the re-evaluation of the role of IL-12 in immune protection and pathology","volume":"51","author":"Gaignage","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1099\/vir.0.037218-0","article-title":"Modulation of lipopolysaccharide receptor expression by lactate dehydrogenase-elevating virus","volume":"93","author":"Su","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrmicro2848","article-title":"Microbial translocation in HIV infection: Causes, consequences and treatment opportunities","volume":"10","author":"Sandler","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Van de Weg, C.A.M., Pannuti, C.S., and de Araujo, E.S.A. (2013). Microbial translocation is associated with extensive immune activation in dengue virus infected patients with severe disease. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002236"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kassa, F.A., Shio, M., Bellemare, M.-J., Faye, B., Ndao, M., and Olivier, M. (2011). New inflammation-related biomarkers during malaria infection. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026495"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1084\/jem.186.12.2051","article-title":"Targeted deletion of the lipopolysaccharide (LPS)-binding protein gene leads to profound suppression of LPS responses ex vivo, whereas in vivo responses remain intact","volume":"186","author":"Wurfel","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/39622","article-title":"Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection","volume":"389","author":"Jack","year":"1997","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1172\/JCI2338","article-title":"LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria","volume":"101","author":"Lamping","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1097\/QAD.0000000000000735","article-title":"Soluble CD14 is a nonspecific marker of monocyte activation","volume":"29","author":"Shive","year":"2015","journal-title":"AIDS"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1086\/515163","article-title":"Endotoxin interactions with lipopolysaccharide-responsive cells","volume":"28","author":"Tobias","year":"1999","journal-title":"Clin. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/infdis\/171.3.639","article-title":"Increased circulating soluble CD14 is associated with high mortality in gram-negative septic shock","volume":"171","author":"Landmann","year":"1995","journal-title":"J. Infect. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/8851\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:36:11Z","timestamp":1760124971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/8851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,16]]},"references-count":35,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24108851"],"URL":"https:\/\/doi.org\/10.3390\/ijms24108851","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,5,16]]}}}