Microbes and Infection最新文献

{"title":"Immunization with a Mu-class glutathione transferase from Echinococcus granulosus induces efficient antibody responses and confers long-term protection against secondary cystic echinococcosis","authors":"Paula Arbildi ,&nbsp;Ana Clara Muniz-Lagos ,&nbsp;Eugenia Fernández ,&nbsp;Rosina Giorgi ,&nbsp;Kai Wiater ,&nbsp;Gustavo Mourglia-Ettlin ,&nbsp;Verónica Fernández","doi":"10.1016/j.micinf.2024.105364","DOIUrl":"10.1016/j.micinf.2024.105364","url":null,"abstract":"<div><p>Cystic echinococcosis, a zoonosis caused by cestodes belonging to the <em>Echinococcus granulosus sensu lato</em> (s.l.) genetic complex, affects humans and diverse livestock species. Although a veterinary vaccine exhibiting high levels of antibody-mediated protection has successfully reached the market, the large genetic diversity among parasite isolates and their particular host preferences, makes still necessary the search for novel vaccine candidates. Glutathione transferases (GSTs) constitute attractive targets for immunoprophylaxis due to their outstanding relevance in helminth detoxification processes, against both exogenous and endogenous stressors. Among the six GSTs known to be expressed in <em>E. granulosus</em> s.l., EgGST1 (Mu-class), EgGST2 (Sigma-class), and EgGST3 (a still non-classifiable isoenzyme), show the highest proteomic expression. Therefore, their recombinant forms -rEgGST1, rEgGST2 and rEgGST3- were herein analyzed regarding their potential to induce long-term antiparasite protection in mice. Only immunization with rEgGST1 induced long-lasting protection; and accordingly, rEgGST1-specific antibodies enhanced the parasite killing through both the classical activation of the host complement system and the antibody-dependent cellular cytotoxicity by macrophages. These results support further testing of rEgGST1 as a vaccine candidate in diverse hosts due to the broad expression of EgGST1 in different parasite stages and tissues.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105364"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A murine model of DC-SIGN humanization exhibits increased susceptibility against SARS-CoV-2","authors":"Yeqing Tu ,&nbsp;Yitai Fang ,&nbsp;Rui Zheng ,&nbsp;Dan Lu,&nbsp;Xiaolan Yang,&nbsp;Liangyan Zhang,&nbsp;Deyu Li,&nbsp;Yakun Sun,&nbsp;Wenjing Yu,&nbsp;Deyan Luo,&nbsp;Hui Wang","doi":"10.1016/j.micinf.2024.105344","DOIUrl":"10.1016/j.micinf.2024.105344","url":null,"abstract":"<div><p>To generate a new murine model for virus, DC-SIGN gene in murine was humanized. In this study, we successfully generated a humanized C57BL/6N mouse model expressing human DC-SIGN (hDC-SIGN) using CRISPR/Cas9 technology, and evaluated its characters and susceptibility to virus. The humanized mice could survival as usual, and with normal physiological index just like the wild-type mice. Whereas, we found significant differences in the intestinal flora and metabolic profiles between wild-type mice and humanized mice. Following intranasal infection with SARS-CoV-2, hDC-SIGN mice exhibited significantly increased viral loads in the lungs and nasal turbinates, along with more severe lung damage. This phenomenon may be associated with differential lipid metabolism and Fcγ receptor-mediated phagocytosis in two mouse models. This study provides a useful tool for investigating the mechanisms of coronavirus infection and potential drug therapies against novel coronavirus.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105344"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140758257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAPK/ERK activation in macrophages promotes Leishmania internalization and pathogenesis","authors":"Umaru Barrie ,&nbsp;Katherine Floyd ,&nbsp;Arani Datta ,&nbsp;Dawn M. Wetzel","doi":"10.1016/j.micinf.2024.105353","DOIUrl":"10.1016/j.micinf.2024.105353","url":null,"abstract":"<div><p>The obligate intracellular parasite <em>Leishmania</em> binds several receptors to trigger uptake by phagocytic cells, ultimately resulting in visceral or cutaneous leishmaniasis. A series of signaling pathways in host cells, which are critical for establishment and persistence of infection, are activated during <em>Leishmania</em> internalization. Thus, preventing <em>Leishmania</em> uptake by phagocytes could be a novel therapeutic strategy for leishmaniasis. However, the host cellular machinery mediating promastigote and amastigote uptake is not well understood. Here, using small molecule inhibitors of Mitogen-activated protein/Extracellular signal regulated kinases (MAPK/ERK), we demonstrate that ERK1/2 mediates <em>Leishmania amazonensis</em> uptake and (to a lesser extent) phagocytosis of beads by macrophages. We find that inhibiting host MEK1/2 or ERK1/2 leads to inefficient amastigote uptake. Moreover, using inhibitors and primary macrophages lacking spleen tyrosine kinase (SYK) or Abl family kinases, we show that SYK and Abl family kinases mediate Raf, MEK, and ERK1/2 activity and are necessary for uptake. Finally, we demonstrate that trametinib, a MEK1/2 inhibitor used to treat cancer, reduces disease severity and parasite burden in <em>Leishmania</em>-infected mice, even if it is started after lesions develop. Our results show that maximal <em>Leishmania</em> infection requires MAPK/ERK and highlight potential for MAPK/ERK-mediated signaling pathways to be novel therapeutic targets for leishmaniasis.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105353"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141024442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR9 promotes monocytic myeloid-derived suppressor cell induction during JEV infection","authors":"Tingting Lian ,&nbsp;Weijia Zhang ,&nbsp;Haoran Su ,&nbsp;Qing Yu ,&nbsp;Hongxin Zhang ,&nbsp;Qingcui Zou ,&nbsp;Haowei Chen ,&nbsp;Wenjing Xiong ,&nbsp;Nan Zhang ,&nbsp;Ke Wang ,&nbsp;Ling Zhao ,&nbsp;Zhen F. Fu ,&nbsp;Min Cui","doi":"10.1016/j.micinf.2024.105336","DOIUrl":"10.1016/j.micinf.2024.105336","url":null,"abstract":"<div><p>Myeloid-derived suppressor cells (MDSCs) are a group of heterologous populations of immature bone marrow cells consisting of progenitor cells of macrophages, dendritic cells and granulocytes. Recent studies have revealed that the accumulation of MDSCs in the mouse spleen plays a pivotal role in suppressing the immune response following JEV infection. However, the mechanisms by which JEV induces MDSCs are poorly understood. Here, it was found that JEV infection induces mitochondrial damage and the release of mitochondrial DNA (mtDNA), which further leads to the activation of TLR9. TLR9 deficiency decreases the M-MDSCs population and their suppressive function both in vitro and in vivo. Moreover, the increase of MHCⅡ expression on antigen-presenting cells and CD28 expression on T cells in TLR9^−/− mice was positively correlated with M-MDSCs reduction. Accordingly, the survival rate of TLR9^−/− mice dramatically increased after JEV infection. These findings reveal the connections of mitochondrial damage and TLR9 activation to the induction of M-MDSCs during JEV infection.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105336"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absence of PD-L1 signaling hinders macrophage defense against Mycobacterium tuberculosis via upregulating STAT3/IL-6 pathway","authors":"Peijie Qu ,&nbsp;Xinyu Li ,&nbsp;Weihuang Liu ,&nbsp;Fangting Zhou ,&nbsp;Xiaoxu Xu ,&nbsp;Jun Tang ,&nbsp;Mengmeng Sun ,&nbsp;Junli Li ,&nbsp;Haifeng Li ,&nbsp;Yunlin Han ,&nbsp;Chengjun Hu ,&nbsp;Yueshan Lei ,&nbsp;Qin Pan ,&nbsp;Lingjun Zhan","doi":"10.1016/j.micinf.2024.105352","DOIUrl":"10.1016/j.micinf.2024.105352","url":null,"abstract":"<div><p>The blockade of programmed death-ligand 1 (PD-L1) pathway has been clinically used in cancer immunotherapy, while its effects on infectious diseases remain elusive. Roles of PD-L1 signaling in the macrophage-mediated innate immune defense against <em>M.tb</em> is unclear. In this study, the outcomes of tuberculosis (TB) in wild-type (WT) mice treated with anti-PD-1/PD-L1 therapy and macrophage-specific <em>Pdl1</em>-knockout (<em>Pdl1</em>^{<em>ΔΜΦ</em>}) mice were compared. Treatment with anti-PD-L1 or anti-PD-1 benefited protection against <em>M.tb</em> infection in WT mice, while <em>Pdl1</em>^{<em>ΔΜΦ</em>} mice exhibited the increased susceptibility to <em>M.tb</em> infection. Mechanistically, the absence of PD-L1 signaling impaired <em>M.tb</em> killing by macrophages. Furthermore, elevated STAT3 activation was found in PD-L1-deficient macrophages, leading to increased interleukin (IL)-6 production and reduced inducible nitric oxide synthase (iNOS) expression. Inhibiting STAT3 phosphorylation partially impeded the increase in IL-6 production and restored iNOS expression in these PD-L1-deficient cells. These findings provide valuable insights into the complexity and mechanisms underlying anti-PD-L1 therapy in the context of tuberculosis.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105352"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemozoin-induced IFN-γ production mediates innate immune protection against sporozoite infection","authors":"Adriano Franco ,&nbsp;Yevel Flores-Garcia ,&nbsp;Jarrett Venezia ,&nbsp;Abdel Daoud ,&nbsp;Alan L. Scott ,&nbsp;Fidel Zavala ,&nbsp;David J. Sullivan","doi":"10.1016/j.micinf.2024.105343","DOIUrl":"10.1016/j.micinf.2024.105343","url":null,"abstract":"<div><p>Hemozoin is a crystal synthesized by <em>Plasmodium</em> parasites during hemoglobin digestion in the erythrocytic stage. The hemozoin released when the parasites egress from the red blood cell, which is complexed with parasite DNA, is cleared from the circulation by circulating and tissue-resident monocytes and macrophages, respectively. Recently, we reported that intravenous administration of purified hemozoin complexed with <em>Plasmodium berghei</em> DNA (Hz^{<em>PbDNA</em>}) resulted in an innate immune response that blocked liver stage development of sporozoites that was dose-dependent and time-limited. Here, we further characterize the organismal, cellular, and molecular events associated with this protective innate response in the liver and report that a large proportion of the IV administered Hz^PbDNA localized to F4/80⁺ cells in the liver and that the rapid and strong protection against liver-stage development waned quickly such that by 1 week post-Hz^PbDNA treatment animals were fully susceptible to infection. RNAseq of the liver after IV administration of Hz^PbDNA demonstrated that the rapid and robust induction of genes associated with the acute phase response, innate immune activation, cellular recruitment, and IFN-γ signaling observed at day 1 was largely absent at day 7. RNAseq analysis implicated NK cells as the major cellular source of IFN-γ. <em>In vivo</em> cell depletion and IFN-γ neutralization experiments supported the hypothesis that tissue-resident macrophages and NK cells are major contributors to the protective response and the NK cell-derived IFN-γ is key to induction of the mechanisms that block sporozoite development in the liver. These findings advance our understanding of the innate immune responses that prevent liver stage malaria infection.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105343"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S128645792400073X/pdfft?md5=883302df781e2282a7fcf1112879de7f&pid=1-s2.0-S128645792400073X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140783816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Mycoplasma pneumoniae to bypass the association with Guillain-Barré syndrome","authors":"Alicia Broto ,&nbsp;Carlos Piñero-Lambea ,&nbsp;Carolina Segura-Morales ,&nbsp;Anne P. Tio-Gillen ,&nbsp;Wendy W.J. Unger ,&nbsp;Raul Burgos ,&nbsp;Rocco Mazzolini ,&nbsp;Samuel Miravet-Verde ,&nbsp;Bart C. Jacobs ,&nbsp;Josefina Casas ,&nbsp;Ruth Huizinga ,&nbsp;Maria Lluch-Senar ,&nbsp;Luis Serrano","doi":"10.1016/j.micinf.2024.105342","DOIUrl":"10.1016/j.micinf.2024.105342","url":null,"abstract":"<div><p>A non-pathogenic <em>Mycoplasma pneumoniae</em>-based chassis is leading the development of live biotherapeutic products (LBPs) for respiratory diseases. However, reports connecting Guillain-Barré syndrome (GBS) cases to prior <em>M. pneumoniae</em> infections represent a concern for exploiting such a chassis. Galactolipids, especially galactocerebroside (GalCer), are considered the most likely <em>M. pneumoniae</em> antigens triggering autoimmune responses associated with GBS development. In this work, we generated different strains lacking genes involved in galactolipids biosynthesis. Glycolipid profiling of the strains demonstrated that some mutants show a complete lack of galactolipids. Cross-reactivity assays with sera from GBS patients with prior <em>M. pneumoniae</em> infection showed that certain engineered strains exhibit reduced antibody recognition. However, correlation analyses of these results with the glycolipid profile of the engineered strains suggest that other factors different from GalCer contribute to sera recognition, including total ceramide levels, dihexosylceramide (DHCer), and diglycosyldiacylglycerol (DGDAG). Finally, we discuss the best candidate strains as potential GBS-free <em>Mycoplasma</em> chassis.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105342"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924000728/pdfft?md5=1c1e1875b18743a7ff8d13cdc9205302&pid=1-s2.0-S1286457924000728-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary prophylaxis for Clostridioides difficile infection for patients on non-C. difficile antibiotics: a retrospective cohort study","authors":"Ronza Najjar-Debbiny ,&nbsp;Ofra Barnett-Griness ,&nbsp;Anat Arbel ,&nbsp;Shai Cohen ,&nbsp;Gabriel Weber ,&nbsp;Maisam Amar ,&nbsp;Rabah Yassin ,&nbsp;Inbal Greenfeld ,&nbsp;Shereen Shehadeh ,&nbsp;Walid Saliba","doi":"10.1016/j.micinf.2024.105349","DOIUrl":"10.1016/j.micinf.2024.105349","url":null,"abstract":"<div><h3>Objectives</h3><p>Recurrent <em>Clostridioides difficile</em> infection (CDI) poses healthcare challenges and morbidity. Preventing recurrence with prophylactic oral CDI antibiotics lack consensus.</p></div><div><h3>Methods</h3><p>We used data from the largest healthcare provider in Israel to identify all adults aged 18 years or older diagnosed with a first episode of CDI (Index CDI) between February 2018 and December 2022 and subsequently received a non-CDI antibiotic within 2–8 weeks. Patients who received a concurrent prophylactic CDI antibiotic constituted the CDI prophylaxis group. Multivariable Cox proportional hazard regression models were used to examine the association of secondary CDI prophylaxis with CDI recurrence according to the severity of the index CDI (primary objective) and with 4- and 8-week all-cause mortality (secondary objective).</p></div><div><h3>Results</h3><p>A total of 434 eligible patients were included. Among them, 327 did not receive CDI antibiotic prophylaxis, while 107 did. CDI antibiotic prophylaxis was associated with a significant risk reduction of CDI recurrence with an adjusted HR of 0.51 (95% CI, 0.27–0.97). The magnitude of the association was modified by the severity of the index CDI episode (P for interaction 0.0182). Specifically, the HR for recurrence was 0.163 (95% CI 0.045–0.593) for non-severe CDI, and 1.242 (95% CI 0.524–2.946) for severe CDI. No significant association was found between CDI antibiotic prophylaxis and 4–8 weeks mortality.</p></div><div><h3>Conclusion</h3><p>Secondary prophylaxis with CDI antibiotics appears to be associated with a reduced risk of recurrence in patients with previous non-severe CDI episode. Further studies are needed to confirm this finding.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105349"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome profiles of macrophages upon infection by morphotypic smooth and rough variants of Mycobacterium abscessus","authors":"Nishant Nandanwar ,&nbsp;Joy E. Gibson ,&nbsp;Michael N. Neely","doi":"10.1016/j.micinf.2024.105367","DOIUrl":"10.1016/j.micinf.2024.105367","url":null,"abstract":"<div><p><em>Mycobacterium abscessus</em> (Mab) infection can be deadly in patients with chronic lung diseases like cystic fibrosis (CF). In vitro and in vivo, Mab may adopt a smooth (S) or rough (R) morphotype, the latter linked to more severe disease conditions. In vitro studies revealed differences in pathogenicity and immune response to S and R morphotypes. We propose that in vivo both morphotypes exist and may transiently switch depending on the environment, having important pathogenic and immunologic consequences. This can be modeled by morphotypic S and R variants of Mab selected based on in vitro growth conditions. Here, we report the first analysis of early transcriptional events in mouse bone marrow derived macrophages (BMDMs) upon infection with media-selected interchangeable Mab-S and Mab-R morphotypes.</p><p>The early transcriptional events after infection with both morphotypes showed considerable overlap of the pro-inflammatory genes that were differentially regulated compared to the uninfected macrophages. We also observed signature genes significantly differentially regulated in macrophages during infection of media-selected morphotypic Mab-S and Mab-R variants. In conclusion, media-selected Mab-S and Mab-R behave in a similar fashion to stable S and R types with respect to pathogenesis and immune response, serving as a useful model for environmentally influenced morphotype selection.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105367"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924001035/pdfft?md5=fc1e0aa20526d71d120459a9ec46f39a&pid=1-s2.0-S1286457924001035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicentric investigations of the role in the disease severity of accelerated phospholipid changes in COVID-19 patient airway","authors":"Christie Mitri ,&nbsp;François Philippart ,&nbsp;Emmanuelle Sacco ,&nbsp;Stéphane Legriel ,&nbsp;Nathalie Rousselet ,&nbsp;Gabrielle Dupuis ,&nbsp;Benoît Colsch ,&nbsp;Harriet Corvol ,&nbsp;Lhousseine Touqui ,&nbsp;Olivier Tabary","doi":"10.1016/j.micinf.2024.105354","DOIUrl":"10.1016/j.micinf.2024.105354","url":null,"abstract":"<div><h3>Context</h3><p>The changes in host membrane phospholipids are crucial in airway infection pathogenesis. Phospholipase A2 hydrolyzes host cell membranes, producing lyso-phospholipids and free fatty acids, including arachidonic acid (AA), which contributes significantly to lung inflammation.</p></div><div><h3>Aim</h3><p>Follow these changes and their evolution from day 1, day 3 to day 7 in airway aspirates of 89 patients with COVID-19-associated acute respiratory distress syndrome and examine whether they correlate with the severity of the disease. The patients were recruited in three French intensive care units. The analysis was conducted from admission to the intensive care unit until the end of the first week of mechanical ventilation.</p></div><div><h3>Results</h3><p>In the airway aspirates, we found significant increases in the levels of host cell phospholipids, including phosphatidyl-serine and phosphatidyl-ethanolamine, and their corresponding lyso-phospholipids. This was accompanied by increased levels of AA and its inflammatory metabolite prostaglandin E2 (PGE2). Additionally, enhanced levels of ceramides, sphingomyelin, and free cholesterol were observed in these aspirates. These lipids are known to be involved in cell death and/or apoptosis, whereas free cholesterol plays a role in virus entry and replication in host cells. However, there were no significant changes in the levels of dipalmitoyl-phosphatidylcholine, the major surfactant phospholipid. A correlation analysis revealed an association between mortality risk and levels of AA and PGE2, as well as host cell phospholipids.</p></div><div><h3>Conclusion</h3><p>Our findings indicate a correlation between heightened cellular phospholipid modifications and variations in AA and PGE2 with the severity of the disease in patients. Nevertheless, there is no indication of surfactant alteration in the initial phases of the illness.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105354"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}