Infection and Immunity最新文献

{"title":"CRISPR-based genetic tools for the study of host-microbe interactions.","authors":"Martin Echavarria Galindo, Yong Lai","doi":"10.1128/iai.00510-24","DOIUrl":"https://doi.org/10.1128/iai.00510-24","url":null,"abstract":"<p><p>CRISPR-based genetic tools have revolutionized our ability to interrogate and manipulate genes. These tools can be applied to both host and microbial cells, and their use can enhance our understanding of the dynamic nature of host-microbe interactions by uncovering their genetic underpinnings. As reviewed here, CRISPR-based tools are being used to explore the microbiome in an efficient, accurate, and high-throughput manner. By employing CRISPR screens, targeted genome editing, and recording systems to the study of host cells and microorganisms, we can gain critical insights into host defense mechanisms, potential vulnerabilities, and microbial pathogenesis, as well as essential or condition-specific genes involved in host-microbe interactions. Additionally, CRISPR-based genetic tools are being used in animal models to study host-microbe interactions <i>in vivo</i>. Recent advancements in CRISPR-derived technology can be combined with emerging techniques, such as single-cell RNA sequencing, to examine the complex interactions between hosts and microbes, shedding light on the role of the microbiome in health and disease. This review aims to provide a comprehensive overview of how these cutting-edge genetic tools are being used to investigate host-microbial systems, as well as their current limitations. Current research is likely to yield even more advanced genetic toolkits than those presently available, and these can serve researchers in identifying and exploring new therapeutic targets for diseases related to host-microbe interactions.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0051024"},"PeriodicalIF":2.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infections as ecosystems: community metabolic interactions in microbial pathogenesis.","authors":"Aanuoluwa E Adekoya, Shannon R West, Sydney K Arriaga, Carolyn B Ibberson","doi":"10.1128/iai.00530-24","DOIUrl":"https://doi.org/10.1128/iai.00530-24","url":null,"abstract":"<p><p>Microbes rarely exist alone; instead, they live in dynamic multi-species communities with a range of metabolic capacities. To establish within a polymicrobial community, an organism must compete with the other members of the community for space and nutrients. In addition, microbes form complex metabolic interdependencies in polymicrobial environments, and these nutrient exchanges are central to overall community function. Interactions between microbial community members dictate key processes, including nutrient cycling, tolerance to disturbances, and disease progression, and these interactions are known to depend on the environment in which they are measured. Therefore, understanding these ecological interactions is fundamental to our understanding of community composition, function, and impacts on disease. In this mini-review, we will describe the mechanisms microbes use to exchange nutrients in host-associated environments, with a focus on the oral and respiratory tracts. We will particularly emphasize the environmental factors that influence community composition and how interactions between organisms, ranging from cooperation to competition, impact nutrient bioavailability and overall community function during infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0053024"},"PeriodicalIF":2.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-species protection suggests <i>Entamoeba histolytica</i> trogocytosis enables complement resistance through the transfer of negative regulators of complement activation.","authors":"Maura C Ruyechan, Wesley Huang, Katherine S Ralston","doi":"10.1128/iai.00220-25","DOIUrl":"https://doi.org/10.1128/iai.00220-25","url":null,"abstract":"<p><p><i>Entamoeba histolytica</i> is a major cause of diarrheal disease. <i>E. histolytica</i> trophozoites (\"amoebae\") can invade the intestine and disseminate via the bloodstream, resisting complement lysis through unknown mechanisms. Amoebae kill human cells by performing trogocytosis. After performing trogocytosis, amoebae display human proteins on their own surface and are resistant to lysis by human serum. In this study, we sought to further evaluate the mechanism by which amoebae resist complement lysis. To test if complement is responsible for lysis of amoebae, C3-depleted serum was compared to replete serum, and C3 was indeed required for lysis. Amoebae were allowed to perform trogocytosis of human cells and exposed to mouse serum. Although they had performed trogocytosis on a different species than the source of the serum, they were protected from lysis. To test if the protection from lysis by mouse serum was due to the functional interchangeability of human and mouse complement pathway proteins, human CD46 or CD55 (negative regulators of complement activation) were exogenously expressed. Amoebae that expressed human CD46 or CD55 were protected from lysis by mouse serum, indicating that display of human proteins was sufficient to inhibit mouse complement activation. Finally, amoebae were allowed to perform trogocytosis of a cell type in which the complement pathway is not conserved, and they did not become resistant to lysis. Overall, these findings are consistent with the model that trogocytosis enables amoebic acquisition and display of host proteins, including negative regulators of the complement pathway, that provide protection from complement lysis. Since other microbes can perform trogocytosis, this novel mechanism for complement resistance might apply to other infections.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0022025"},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tick-borne coinfections modulate CD8⁺ T cell response and progressive leishmaniosis.","authors":"Breanna M Scorza, Danielle Pessôa-Pereira, Felix Pabon-Rodriguez, Erin A Beasley, Kurayi Mahachi, Arin D Cox, Eric Kontowicz, Tyler Baccam, Geneva Wilson, Max C Waugh, Shelbe Vollmer, Angela Toepp, Kavya Raju, Ogechukwu C Chigbo, Jonah Elliff, Greta Becker, Karen I Cyndari, Serena Tang, Grant Brown, Christine A Petersen","doi":"10.1128/iai.00182-25","DOIUrl":"https://doi.org/10.1128/iai.00182-25","url":null,"abstract":"<p><p><i>Leishmania infantum</i> causes human visceral leishmaniasis and leishmaniosis (CanL) in reservoir host, dogs. As infection progresses to disease in both humans and dogs, there is a shift from controlling type 1 immunity to a regulatory, exhausted T cell phenotype. In endemic areas, the association between tick-borne coinfections (TBCs) and <i>Leishmania</i> diagnosis and/or clinical severity has been demonstrated. To identify immune factors correlating with disease progression, we prospectively evaluated a cohort of <i>L. infantum</i>-infected dogs from 2019 to 2022. The cohort was TBC-negative with asymptomatic leishmaniosis at the time of enrollment. We measured TBC serology, anti-<i>Leishmania</i> antigen T cell immunity, CanL serological response, parasitemia, and disease severity to probe how nascent TBC perturbs the immune state. At the conclusion, TBC+ dogs with CanL experienced greater increases in anti-<i>Leishmania</i> antibody reactivity and parasite burden compared to dogs that did not have incident TBC during the study. TBC+ dogs were twice as likely to experience moderate (LeishVet stage 2) or severe/terminal disease (LeishVet stage 3/4). Prolonged exposure to TBC was associated with a shift in <i>Leishmania</i> antigen-induced interferon gamma (IFN-γ)/interleukin-10 (IL-10) and enhanced CD8 T cell proliferation. Frequency of proliferating CD8 T cells significantly correlated with parasitemia and antibody reactivity. TBC exacerbated parasite burden and immune exhaustion. These findings highlight the need for combined vector control efforts as prevention programs for dogs in <i>Leishmania</i> endemic areas to reduce transmission to humans. Public health education efforts should aim to increase awareness of the connection between TBC and leishmaniosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0018225"},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional characterization of IdeC, a novel IgG-specific protease of <i>Streptococcus canis</i>.","authors":"Saoirse Walsh, Antje-Maria Lapschies, Vega Miguel-Ruano, María T Batuecas, Iván Acebrón-Ávalos, Thomas P Kohler, Sven Hammerschmidt, Inga Eichhorn, Juan A Hermoso, Marcus Fulde","doi":"10.1128/iai.00248-25","DOIUrl":"https://doi.org/10.1128/iai.00248-25","url":null,"abstract":"<p><p><i>Streptococcus canis</i> is an important opportunistic pathogen of cats, dogs, and cows, which can cause a range of infections, ranging from skin and soft tissue infections to septicemia and endocarditis. As a zoonotic agent, <i>S. canis</i> has also recently been implicated in serious human infections, following trauma or immunosuppression. In this work, we describe a novel protease of <i>S. canis</i>, termed IdeC (<u>I</u>mmunoglobulin G <u>d</u>egrading <u>e</u>nzyme of <i>S. <u>c</u>anis</i>), which may be involved in bacterial immune evasion. The cleaving ability of IdeC against IgG from various species was assessed; this revealed that IdeC successfully cleaved canine, feline, and human IgG. We also confirmed that IdeC is a cysteine protease, similar to IdeS of <i>Streptococcus pyogenes</i>. Investigation of the cleavage site in IgG sequences showed that it is highly conserved across IgGs from all species tested. From this analysis, it was determined that IdeC cleavage occurs between the CH2 and hinge regions of IgG. Interestingly, feline IgG was consistently cleaved with the highest efficiency, with human and canine IgG displaying less efficient cleavage. High-resolution crystal structures of two IdeC constructs provided insights into the catalytic machinery and substrate recognition. Modeling of the full-length IdeC:IgG complexes for human, canine, and feline cases explains the mechanism of action of the protease and reveals the molecular basis for the observed cleavage preference for feline IgG. Understanding and managing <i>S. canis</i> as a pathogen is important in both veterinary and human medicine, as this bacterium underscores the need for awareness of zoonotic transmission.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0024825"},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Edwardsiella ictaluri</i> type III secretion system effector EseG modulates cytoskeletal dynamics and immune response in macrophages.","authors":"Lidiya Dubytska, Ranjan Koirala, Matthew Rogge, Ronald Thune","doi":"10.1128/iai.00525-24","DOIUrl":"https://doi.org/10.1128/iai.00525-24","url":null,"abstract":"<p><p><i>Edwardsiella ictaluri</i> is a gram-negative enteric pathogen responsible for enteric septicemia of catfish. One of the critical virulence factors identified in <i>E. ictaluri</i> is its type III secretion system (T3SS). In this study, we report that the T3SS effector protein EseG requires the small chaperone protein EscB for translocation. EseG shows partial homology to two <i>Salmonella</i> T3SS effectors, SseG and SseF, as well as to the <i>Edwardsiella piscicida</i> effector EseG, all of which also require chaperones for translocation. Functionally, EseG interacts with and inactivates Ras homolog family member A (RhoA), a small GTPase that regulates the dynamic organization of the microtubule and actin cytoskeleton. The cytoskeleton is vital for cell morphology, polarity, adhesion, exocytosis, endocytosis, cytokinesis, and transcriptional control. We demonstrate that inactivation of RhoA by EseG leads to the disassembly of both the microtubule and actin cytoskeleton. Moreover, EseG was found to modulate immune responses by altering the expression of several pro-inflammatory interleukins and transcription factors, as well as cyclooxygenase-2 (COX-2). Reduced expression of COX-2 leads to decreased production of prostaglandin E2, a key mediator of inflammation. Additionally, a Δ<i>eseG</i> mutant strain exhibited reduced virulence and persistence in channel catfish (<i>Ictalurus punctatus</i>), underscoring the importance of EseG in the disease process. Collectively, our data highlight EseG as a critical factor in <i>E. ictaluri</i> pathogenesis, particularly in its ability to modulate host immune responses. By elucidating the function of EseG, this study contributes to a deeper understanding of <i>E. ictaluri</i> pathogenesis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0052524"},"PeriodicalIF":2.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Babich, \"Using exosomes for universal vaccines\".","authors":"Saloni Bhimani, Mariola J Ferraro","doi":"10.1128/iai.00207-25","DOIUrl":"https://doi.org/10.1128/iai.00207-25","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0020725"},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using exosomes for universal vaccines.","authors":"Alfred R Babich","doi":"10.1128/iai.00129-25","DOIUrl":"https://doi.org/10.1128/iai.00129-25","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0012925"},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ficolin-1 in pediatric <i>Plasmodium falciparum</i> malaria and its possible role in parasite clearance and anemia.","authors":"Di Zheng, Natalie Ferrington, Dilini Rathnayake, Wina Hasang, Agersew Alemu, Visopo Harawa, Amalia Karahalios, Phoebe Fitzpatrick, Evelyne Gout, Nicole M Thielens, Karl Seydel, Terrie E Taylor, Wilson Mandala, Stephen J Rogerson, Elizabeth H Aitken, Louise M Randall","doi":"10.1128/iai.00194-25","DOIUrl":"10.1128/iai.00194-25","url":null,"abstract":"<p><p><i>Plasmodium falciparum</i> malaria causes significant disease, especially in young children. A successful immune response to <i>P. falciparum</i> is a major determinant of clinical outcome. The ficolins are a family of lectins that act as pattern recognition molecules and can activate the lectin complement pathway and may promote inflammation and facilitate opsonization and lysis of pathogens. Here, we have investigated the potential roles of ficolin-1 and ficolin-2 in the context of <i>P. falciparum</i> infection. We measured ficolin-1 and ficolin-2 concentrations in plasma from Malawian children presenting with uncomplicated or severe malaria or healthy controls (HCs) by ELISA. Using flow cytometry, we assessed whether ficolin-1 could bind to infected red blood cells (iRBCs) and whether it binds sialic acid on the iRBCs. Ficolin-1 and ficolin-2 plasma levels were measured in children from all clinical groups. Compared to HCs (reference), Ficolin-1 concentrations in plasma were higher in children with uncomplicated (geometric mean ratio: 1.88; 95% confidence interval [CI]: 1.25-2.82) and severe malaria (1.65; 95% CI: 1.10-2.46). Ficolin-1 levels were positively associated with peripheral blood monocyte (1.30; 1.02-1.67) and neutrophil counts (1.06; 1.00-1.13). Ficolin-2 was not associated with malaria. Hemoglobin levels were negatively associated with ficolin-1 (-0.38; -0.68 to -0.09) and ficolin-2 (-0.36; -0.68 to -0.04). Ficolin-1 bound more to iRBCs compared to uninfected RBCs, and binding was reduced in a ficolin-1 mutant that did not bind to sialic acid. These results highlight a largely overlooked role for ficolin-1 in the immune response to <i>P. falciparum</i> infection and point to a potential role for lectins contributing to parasite clearance and anaemia.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0019425"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150379","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":"Characterization of the <i>Listeria monocytogenes</i> PieRS regulon distinguishes the function of the critical secretion chaperone PrsA2 from other regulon members.","authors":"Xiomarie Alejandro-Navarreto, Laty A Cahoon, Nancy E Freitag","doi":"10.1128/iai.00357-24","DOIUrl":"10.1128/iai.00357-24","url":null,"abstract":"<p><p><i>Listeria monocytogenes</i> (<i>Lm</i>) is a gram-positive pathogen that is widespread throughout the environment and known for its ability to infect mammalian hosts following the ingestion of contaminated food. <i>Lm</i> uses a variety of mechanisms to survive challenging conditions experienced both during life in the outside environment and inside of the infected host. We recently described a novel two-component signaling system known as PieRS that regulates the secretion of the chaperone PrsA2, which is essential for bacterial virulence, as well as its related homolog PrsA1 and a variety of gene products of unknown function. Here, we examine the roles of the less characterized PieRS-regulated gene products and contrast their functions with PrsA2 in terms of bacterial survival under stress conditions and virulence in mice. Characterization of targeted in-frame deletion mutants of PieRS regulon members indicates-in contrast to <i>prsA2</i> mutants-minimal contributions to stress survival and bacterial virulence. Modest contributions of select regulon members were associated with <i>Lm</i> colonization of the gastrointestinal tract. The PieRS regulon thus consists of gene products that contribute to <i>Lm</i> physiology in ways that are clearly distinct from PrsA2 and the chaperone's essential function for both stress survival and bacterial virulence.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0035724"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150377","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}