Infection and Immunity最新文献

{"title":"Multi-system dysregulation in placental malaria contributes to adverse perinatal outcomes in mice.","authors":"Phebe Ekregbesi, Brittany Seibert, Maclaine A Parish, Yevel Flores-Garcia, Patrick S Creisher, Joseph P Hoffmann, Jennifer A Liu, Cory Brayton, Fidel Zavala, Sabra L Klein","doi":"10.1128/iai.00021-25","DOIUrl":"10.1128/iai.00021-25","url":null,"abstract":"<p><p>Sequestration of <i>Plasmodium</i> parasites in the placental vasculature contributes to increased morbidity and mortality in pregnant compared to non-pregnant patients in malaria-endemic regions. In this study, outbred pregnant CD1 mice with semi-allogeneic fetuses were infected with transgenic <i>Plasmodium berghei</i> or mock inoculated by mosquito bite at either embryonic day (E)6 (first trimester-equivalent) or 10 (second trimester-equivalent) and were compared to non-pregnant females. <i>P. berghei</i>-infected mosquitoes had greater biting avidity for E10 dams than uninfected mosquitoes, which was not apparent for E6 dams nor non-pregnant females. Infected E10 dams had greater numbers of parasites than E6 dams in the uterus and spleen, but not in the blood or liver. While parasites were found in placentas, no parasites were present in fetuses. Maternal infection at E6 caused greater maternal morbidity, with greater rates of fetal reabsorption and stillbirths than at E10. Infection at E10 caused adverse offspring outcomes, including growth restriction. To identify possible mechanisms of adverse offspring outcomes, E10 dams were euthanized during peak parasitemia (8 days postinfection [dpi]), and outcomes were compared to mock-infected dams. <i>P. berghei</i> caused significant systemic maternal immune activation with elevated circulating lymphocytes, eosinophils, and neutrophils and splenic cytokine concentrations. <i>P. berghei</i> infection at E10 increased corticosterone and decreased progesterone concentrations, which could contribute to adverse perinatal outcomes through immunomodulation. There were limited changes in the maternal fecal microbiome after <i>P. berghei</i> infection. Mosquito bite infection of outbred dams with <i>P. berghei</i> causes placental malaria and provides a novel, tractable model to investigate therapeutic treatments.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0002125"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal antibody neutralizes <i>Staphylococcus aureus</i> serine protease-like protein B (SplB)-induced pathology.","authors":"Jawad Iqbal, Jessica von Fournier, Nico Wittmann, Murthy N Darisipudi, Daniel M Mrochen, Bojan Smiljanov, Kristin Surmann, Gina Wockenfuß, Leif Steil, Thomas P Kohler, Felix L Glinka, Shruthi Peringathara, Christopher Saade, Liliane M Fernandes, Uwe Bornscheuer, Christoph A Reichel, Barbara M Bröker, Dina Raafat, Silva Holtfreter","doi":"10.1128/iai.00171-25","DOIUrl":"10.1128/iai.00171-25","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> is a versatile pathogen, renowned for its arsenal of virulence and immune evasion factors. Several <i>S. aureus</i> virulence factors have been targeted in vaccination trials; however, so far, without success. Promising new vaccine candidates are the staphylococcal serine protease-like proteins (Spl A-F), which are involved in the pathogenesis and immune evasion of <i>S. aureus</i>. SplB, for instance, promotes type 2 immune responses and inactivates human complement factors. In this study, we report on the production and characterization of a murine monoclonal antibody (mAb) against SplB. The murine anti-SplB mAb α-SplB1 was produced by hybridoma technology, and its binding characteristics were investigated using enzyme-linked immunosorbent assay (ELISA), Western blot, and MicroScale Thermophoresis. Its neutralizing capacity was determined in a fluorogenic substrate assay, Western blot, and a murine vascular leakage model. α-SplB1 bound to recombinant SplB with high specificity, showing no cross-reactivity to other Spls or secreted proteins of <i>S. aureus</i>. MicroScale Thermophoresis revealed a K_D value of 37.9 nM for the α-SplB1:SplB interaction. α-SplB1 neutralized the enzymatic activity of SplB <i>in vitro</i> in a dose-dependent manner, yielding complete neutralization at a twofold molar excess of the antibody. In a murine vascular leakage model, the antibody completely abolished SplB-mediated endothelial damage. In summary, we produced a neutralizing mAb against the staphylococcal protease SplB, which merits further investigation as a candidate for the immunotherapy of SplB-induced pathologies.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0017125"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the life cycle, host cell tropism, and infection amplification of <i>Leishmania</i> spp.","authors":"Anna Luiza Silva-Moreira, Artur Metzker Serravite, Laura Valéria Rios-Barros, Juliana Perrone Bezerra de Menezes, Maria Fátima Horta, Thiago Castro-Gomes","doi":"10.1128/iai.00123-25","DOIUrl":"10.1128/iai.00123-25","url":null,"abstract":"<p><p>The genus <i>Leishmania</i> comprises several species of digenetic protozoan parasites that cause a spectrum of diseases known as leishmaniases, which are transmitted to humans and other mammals through the bite of hematophagous female sand flies. <i>Leishmania</i> spp. and their invertebrate vectors are widely distributed across the globe, putting more than a billion people at risk. Once inside mammalian hosts, these intracellular parasites reside within parasitophorous vacuoles of host cells. Although macrophages are the primary infected cells in lesions, <i>Leishmania</i> can also infect other cell types, whose roles in maintaining the parasite's life cycle and contributing to pathogenesis remain unclear. Similarly, the processes governing parasite dissemination from the initial infection site in the skin to internal organs, as well as the mechanisms driving the infection of new cells, are still under investigation. In this review, we underscore some existing gaps in <i>Leishmania</i>'s life cycle, discussing i) the various cell types that serve as host cells for the parasite and their potential roles in the disease, ii) the mechanisms that might contribute to infection amplification, iii) the strategies possibly involved in dissemination and visceralization, iv) the mechanisms driving the generation of super-infective vectors, and v) the occurrence of a mating stage in the cycle. Altogether, these aspects may reshape our perspective on the basic biology of <i>Leishmania</i>, deepening our understanding of the host-parasite relationship and hopefully opening avenues toward a better understanding of the disease.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0012325"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxygen and immunity to <i>Leishmania</i> infection.","authors":"Bridget A Bowman, Fernanda O Novais","doi":"10.1128/iai.00504-24","DOIUrl":"10.1128/iai.00504-24","url":null,"abstract":"<p><p>Oxygen availability plays a fundamental role in shaping immune responses to infections. Leishmaniasis, a disease caused by protozoan parasites of the genus <i>Leishmania</i>, manifests in a spectrum of clinical outcomes, ranging from localized cutaneous lesions to life-threatening visceral infections. Like many infections and chronic diseases, <i>Leishmania</i>-infected tissues are characterized by hypoxia. Despite the recognized importance of oxygen in immune regulation, our understanding of how hypoxia shapes the immune landscape in leishmaniasis remains in its early stages. Collectively, the published studies in leishmaniasis highlight the critical role of oxygen availability and hypoxia-inducible factor (HIF) in orchestrating immune responses, particularly within myeloid cells. Here, we review the literature on how oxygen availability and HIF signaling influence the immune response in leishmaniasis. By consolidating existing findings and identifying gaps in knowledge, we aim to inspire further research into the interplay between oxygen availability, immune function, disease progression, and therapeutic potential in leishmaniasis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0050424"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiating <i>Peromyscus leucopus</i> bone marrow-derived macrophages for characterization of responses to <i>Borrelia burgdorferi</i> and lipopolysaccharide.","authors":"Christopher C Wells, Tanja Petnicki-Ocwieja, Shumin Tan, Stephen C Bunnell, Sam R Telford, Linden T Hu, Jeffrey S Bourgeois","doi":"10.1128/iai.00581-24","DOIUrl":"10.1128/iai.00581-24","url":null,"abstract":"<p><p>Currently, most tools utilized in host-pathogen interaction studies depend on the use of human or mouse (<i>Mus musculus</i>) cells and tissues. While these species have led to countless breakthroughs in our understanding of infectious disease, there are undoubtedly important biological processes that are missed by limiting studies to these two vertebrate species. For instance, it is well-established that a common deermouse in North America, <i>Peromyscus leucopus</i>, has unique interactions with microbes, which likely shape its ability to serve as a critical reservoir for numerous zoonotic pathogens, including a Lyme disease spirochete, <i>Borrelia burgdorferi</i>. In this work, we expand the immunological toolkit to study <i>P. leucopus</i> biology by performing the first differentiation of deermouse bone marrow to macrophages using <i>P. leucopus</i> M-CSF producing HEK293T cells. We find that <i>P. leucopus</i> BMDMs generated through this method behave broadly very similarly to C57BL/6J macrophages generated with the L-929 supernatant, although RNA sequencing revealed modest differences in transcriptomic responses to <i>B. burgdorferi</i> and lipopolysaccharide. In particular, differences in Il-10 induction and caspase expression were observed between the species.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0058124"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the immunomodulatory effects of honeybee venom peptide apamin in <i>Drosophila</i> platforms.","authors":"Yanan Wei, Wenjie Jia, Yanying Sun, Tianmu Zhang, Hongyu Miao, Zekun Wu, Ran Dong, Fangyong Ning, Woo Jae Kim","doi":"10.1128/iai.00131-25","DOIUrl":"10.1128/iai.00131-25","url":null,"abstract":"<p><p>Apamin, an 18-amino-acid honeybee venom peptide, although traditionally recognized for its neurotoxic effects, demonstrates potent antimicrobial properties in our research when genetically expressed in <i>Drosophila</i>. This antimicrobial efficacy is independent of its disulfide bonds and is enhanced when the peptide is membrane-tethered. Apamin selectively inhibits pathogenic bacteria, such as <i>Pseudomonas aeruginosa</i>, <i>Enterococcus faecalis</i>, and <i>Escherichia coli</i>, while promoting beneficial bacteria like <i>Lactobacillus plantarum,</i> thereby improving the gut microbiome. This gut-localized antimicrobial activity is associated with increased intestinal stem cell proliferation, midgut acidification, and enteroendocrine cell calcium signaling. Furthermore, apamin's antimicrobial function relies on specific peptidoglycan recognition proteins, particularly PGRP-LA and PGRP-SCs. Apamin expression alone is sufficient to restore the integrity of the gut barrier compromised by stressful conditions. Ultimately, apamin supplementation enhances honeybee gut health in the presence of ingested bacteria. The expression of other honeybee antimicrobial peptides also significantly reduces bacterial infection in flies. Overall, our study provides a comprehensive understanding of honeybee venom peptides and antimicrobial peptides functions, utilizing the <i>Drosophila</i> model system to unravel their mechanisms of action and therapeutic potential.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0013125"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling reveals immunomodulatory role of IL-33 in ocular bacterial and fungal infections.","authors":"Zeeshan Ahmad, Sukhvinder Singh, Dhanwini Rudraprasad, Joveeta Joseph, Nikhlesh K Singh, Ashok Kumar","doi":"10.1128/iai.00183-25","DOIUrl":"10.1128/iai.00183-25","url":null,"abstract":"<p><p>Bacterial and fungal pathogens are major causes of infectious endophthalmitis following eye surgery or trauma, often leading to vision impairment or blindness. The distinct clinical outcomes observed in bacterial and fungal endophthalmitis suggest differences in host immune responses. To investigate these differences, we utilized cytokine arrays and murine models of bacterial (<i>Staphylococcus aureus</i>) and fungal (<i>Aspergillus fumigatus</i>) endophthalmitis. Our analysis revealed that cytokine responses peaked in bacterial infections at 12-24 h, whereas fungal infections exhibited a delayed peak at 48 h. Several inflammatory mediators, including MMP9, MMP3, CD14, LIX, LCN2, retinol-binding protein 4, ICAM1, and VCAM1, were differentially elevated. Notably, interleukin-33 (IL-33) levels peaked early in bacterial infections but continued to rise throughout all time points in fungal endophthalmitis. Analysis of patient vitreous samples further confirmed higher levels of IL-33 in bacterial (<i>n</i>=40) and fungal (<i>n</i>=20) endophthalmitis cases. Functional studies in IL-33-deficient mice revealed an increased fungal burden and elevated TNF-α and IL-6 levels, but bacterial endophthalmitis severity remains largely unaffected. Additionally, bone marrow-derived macrophages from IL-33^-/- mice exhibited increased cell death in response to fungal and bacterial infection. Our findings reveal divergent innate immune responses between bacterial and fungal endophthalmitis and emphasize the immunomodulatory function of IL-33 in ocular infections.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0018325"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A chronic <i>Pseudomonas aeruginosa</i> mouse lung infection modeling the mucus obstruction, lung function, and inflammation of human cystic fibrosis.","authors":"Mylene Vaillancourt, Sheryl E Fernandes, Diane Aguilar, Anna Clara Milesi Galdino, Peter Jorth","doi":"10.1128/iai.00230-25","DOIUrl":"10.1128/iai.00230-25","url":null,"abstract":"<p><p>Mouse models of cystic fibrosis (CF) have been used to study chronic lung infections; however, these models have lacked the airway mucus that defines human CF pathophysiology and required the use of mucoid <i>Pseudomonas aeruginosa</i>. Alternative models have used either transgenic <i>Scnn1b-Tg</i> mice overexpressing a lung epithelial sodium channel to mimic the mucus-rich CF lung environment, synthetic CF sputum medium (SCFM2) to induce bacterial phenotypes consistent with human CF, or agar beads to promote chronic infections by non-mucoid <i>P. aeruginosa</i>. Here, we combined these alternative models and established a chronic <i>P. aeruginosa</i> lung infection model using SCFM2 agar beads and <i>Scnn1b-</i>Tg mice (SCFM2-<i>Scnn1b-</i>Tg) to recapitulate nutrient and mucus characteristics of the human CF lung environment and test the effects of chronic infections on bacterial burden, lung function, and the immune response. Using wild-type SCFM2-C57BL/6 mice as controls, SCFM2-<i>Scnn1b-</i>Tg mice failed to clear bacterial infections, and lung function measurements showed that infected SCFM2-<i>Scnn1b-</i>Tg mice had decreased inspiratory capacity and compliance, elevated airway resistance, and significantly reduced forced expiratory volumes. Flow cytometry and cytokine arrays showed that, like people with CF, SCFM2-<i>Scnn1b-</i>Tg mice developed inflammation characterized by neutrophil and eosinophil infiltration and Th2 lymphocytic cytokine responses. Chronically infected SCFM2-<i>Scnn1b-</i>Tg mice developed an exacerbated mix of innate and Th1, Th2, and Th17-mediated inflammation, causing higher lung cellular damage and elevated numbers of unusual Siglec F⁺ neutrophils. SCFM2-<i>Scnn1b-</i>Tg mice will be useful for investigating bacterial pathogenesis by non-mucoid <i>P. aeruginosa</i>, including treatments and the roles of Siglec F⁺ neutrophils in CF inflammation.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0023025"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GM-CSF engages multiple signaling pathways to enhance pro-inflammatory cytokine responses in human monocytes during <i>Legionella</i> infection.","authors":"Víctor R Vázquez Marrero, Madison Dresler, Mikel D Haggadone, Allyson Lu, Sunny Shin","doi":"10.1128/iai.00565-24","DOIUrl":"10.1128/iai.00565-24","url":null,"abstract":"<p><p>The proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for host defense against a wide range of pathogens. During infection with the intracellular bacterial pathogen <i>Legionella pneumophila</i>, we previously found that GM-CSF enhances inflammatory cytokine production in murine monocytes and is required for <i>in vivo</i> control of <i>Legionella</i>. It is unclear whether GM-CSF similarly augments cytokine production in human monocytes during bacterial infection. Here, we find that GM-CSF enhances inflammatory cytokine expression in <i>Legionella-</i>infected human monocytes by engaging multiple signaling pathways. <i>Legionella</i>- and Toll-like receptor-dependent NF-[Formula: see text]B signaling is a prerequisite signal for GM-CSF to promote cytokine expression. Then, GM-CSF-driven Janus kinase 2/signal transducer and activator of transcription 5 signaling is required to augment cytokine expression in <i>Legionella</i>-infected human monocytes. We also found a role for phosphatidylinositol-3-kinase/Akt/mTORC1 signaling in GM-CSF-dependent upregulation of cytokine expression. Finally, glycolysis and amino acid metabolism are also critical for GM-CSF to boost cytokine gene expression. Our findings show that GM-CSF-mediated enhancement of cytokine expression in infected human monocytes is regulated by multiple signaling pathways, thereby allowing the host to fine-tune antibacterial immunity.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0056524"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parenteral vaccination with recombinant EtpA glycoprotein impairs enterotoxigenic <i>E. coli</i> colonization.","authors":"Tim J Vickers, David P Buckley, Nazia Khatoon, Alaullah Sheikh, Bipul Setu, Zachary T Berndsen, James M Fleckenstein","doi":"10.1128/iai.00601-24","DOIUrl":"10.1128/iai.00601-24","url":null,"abstract":"<p><p>Enterotoxigenic <i>E. coli</i> (ETEC) causes hundreds of millions of cases of acute diarrheal illness in low- and middle-income regions, disproportionately in young children. To date, there is no licensed, broadly protective vaccine against these common but antigenically heterogeneous pathogens. One of the more highly conserved antigens of ETEC, EtpA, is an extracellular glycoprotein adhesin that preferentially binds to A blood group glycans on intestinal epithelia. EtpA contributes to increased severity of illness in A blood group individuals, elicits robust serologic and fecal antibody responses following infection, and has been associated with protection against subsequent infection. However, its utility as a protective antigen needs further examination. In the present studies, we examined whether parenteral vaccination with recombinant EtpA (rEtpA) could afford protection against intestinal colonization in a murine model of ETEC infection. Here, we demonstrate that intramuscular vaccination with rEtpA, adjuvanted with double mutant LT (dmLT), primes IgG predominant mucosal antibody responses to ETEC challenge. Notably, however, both antibody levels and avidity, as well as protection, were dependent on the vaccination schedule. Likewise, through electron microscopy polyclonal epitope mapping (EMPEM), we observed a different repertoire of epitopes targeted by antibodies after a more protracted vaccination schedule. Next, we explored the utility of IM immunization with alum-adjuvanted rEtpA. This elicited strong serologic and fecal IgG responses. Although accompanied by negligible IgA mucosal responses, EtpA alum-adjuvanted IM vaccination nevertheless protected against ETEC intestinal colonization. Collectively, these data suggest that EtpA could expand the portfolio of antigens targeted in ETEC subunit vaccine development.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0060124"},"PeriodicalIF":2.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}