Infection and Immunity最新文献

{"title":"NLRP3 inflammasome inhibition decreases <i>Schistosomiasis japonica</i>-induced granulomatous inflammation and fibrosis in BALB/c mice.","authors":"Yaqi Lu, Jing Liu, Wangxian Tang, Heng Zhang","doi":"10.1128/iai.00055-24","DOIUrl":"https://doi.org/10.1128/iai.00055-24","url":null,"abstract":"<p><p>To research the role of the NLRP3 inflammasome in <i>Schistosoma japonicum</i>-induced granuloma formation and liver fibrosis. In <i>in vivo</i> tests, BALB/c mice were used. shNLRP3 plasmid based on adeno-associated virus serotype 8 (AAV8-shNLRP3) was injected to block NLRP3 inflammasome via tail vein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected to assess liver injury. H&E staining was used for routine histopathological assessment; Masson's trichrome staining was used to detect fibrous tissues and collagen fibers. Hepatic expression of NLRP3, procaspase-1, bioactive caspase-1, collagen-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and α-smooth muscle actin (α-SMA) were detected by western blot. Serum levels of IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The inflammatory cell infiltration and hepatic expression of IL-1β around the granuloma were detected by immunohistochemistry staining. Treatment of <i>S. japonicum</i> infected mice with AAV8-shNLRP3 significantly reduced the hepatic levels of bioactive caspase-1 and IL-1β, as well as circulating IL-1β concentrations, while reducing the amounts of myeloperoxidase (MPO) and F4/80 positive cells around the granuloma. Moreover, collagen deposition, TIMP-1, and α-SMA, which are markers of hepatic stellate cell (HSC) activation, were reduced around the liver granuloma. These findings highlight a therapeutic potential of AAV8-shNLRP3 in schistosomiasis cirrhosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999846","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":"Protective innate immunity against <i>Pneumocystis</i> does not require Stat6-dependent macrophage polarization.","authors":"T Mousso, S J Pollock, P C Inzerillo, F Gigliotti, T W Wright","doi":"10.1128/iai.00222-24","DOIUrl":"https://doi.org/10.1128/iai.00222-24","url":null,"abstract":"<p><p><i>Pneumocystis</i> species are respiratory fungal pathogens that cause life-threatening opportunistic infections in immunocompromised hosts. <i>Pneumocystis</i> typically evade pulmonary innate immunity but are efficiently eradicated by a functional adaptive immune response. FVB/NJ mice are unique in that they display protective alveolar macrophage-dependent innate immunity against <i>Pneumocystis</i>, and remain resistant to infection even in the absence of CD4⁺ T lymphocyte function. FVB/NJ alveolar macrophages (AMs) were found to display an M2-biased phenotype at baseline, which was potentiated after stimulation with <i>Pneumocystis</i>, suggesting that macrophage polarization may dictate the outcome of the <i>Pneumocystis</i>-macrophage interaction. To determine whether Stat6, a key global regulator of M2 polarization, was required for FVB/NJ innate immunity, FVB Stat6^-/- mice were generated. FVB Stat6-deficient AMs were markedly impaired in their ability to polarize to an M2 phenotype when stimulated with Th2 cytokines. However, FVB Stat6^-/- mice remained highly resistant to infection, indicating that Stat6 signaling is dispensable for innate FVB/NJ resistance. Despite the loss of Stat6 signaling, primary AMs from FVB Stat6^-/- mice maintained baseline expression of M2 markers, and also strongly upregulated M2-associated genes following direct stimulation with <i>Pneumocystis</i>. Additional FVB/NJ knockout strains were generated, but only FVB MerTK^-/- mice showed a marginally increased susceptibility to <i>Pneumocystis</i> infection. Together, these findings demonstrate that effective FVB/NJ innate immunity against <i>Pneumocystis</i> does not require Stat6 signaling and suggest that alternative pathways regulate M2 bias and macrophage-mediated innate resistance in FVB/NJ mice.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987856","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":"RSV enhances <i>Staphylococcus aureus</i> bacterial growth in the lung.","authors":"Helen E Rich, Simran Bhutia, Francina Gonzales de Los Santos, Gabrielle P Entrup, Helen I Warheit-Niemi, Stephen J Gurczynski, Monica Bame, Michael T Douglas, Susan B Morris, Rachel L Zemans, Nicholas W Lukacs, Bethany B Moore","doi":"10.1128/iai.00304-24","DOIUrl":"10.1128/iai.00304-24","url":null,"abstract":"<p><p>Patients coinfected with respiratory syncytial virus (RSV) and bacteria have longer hospital stays, higher risk of intensive care unit admission, and worse outcomes. We describe a model of RSV line 19F/methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) USA300 coinfection that does not impair viral clearance, but prior RSV infection enhances USA300 MRSA bacterial growth in the lung. The increased bacterial burden post-RSV correlates with reduced accumulation of neutrophils and impaired bacterial killing by alveolar macrophages. Surprisingly, reduced neutrophil accumulation is likely not explained by reductions in phagocyte-recruiting chemokines or alterations in proinflammatory cytokine production compared with mice infected with <i>S. aureus</i> alone. Neutrophils from RSV-infected mice retain their ability to migrate toward chemokine signals, and neutrophils from the RSV-infected lung are better able to phagocytize and kill <i>S. aureus ex vivo</i> on a per cell basis. In contrast, while alveolar macrophages could ingest USA300 post-RSV, intracellular bacterial killing was impaired. The RSV/<i>S. aureus</i> coinfected lung promotes a state of overactivation in neutrophils, demonstrated by increased production of reactive oxygen species (ROS) that can drive formation of neutrophil extracellular traps (NETs), resulting in cell death. Mice with RSV/<i>S. aureus</i> coinfection had increased extracellular DNA and protein in bronchoalveolar lavage fluid and histological evidence confirmed NETosis <i>in vivo</i>. Taken together, these data highlight that prior RSV infection can prime the overactivation of neutrophils leading to cell death that impairs neutrophil accumulation in the lung. Additionally, alveolar macrophage killing of bacteria is impaired post-RSV. Together, these defects enhance USA300 MRSA bacterial growth in the lung post-RSV.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987857","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":"The type II secretion system as an underappreciated and understudied mediator of interbacterial antagonism.","authors":"Nicholas P Cianciotto","doi":"10.1128/iai.00207-24","DOIUrl":"10.1128/iai.00207-24","url":null,"abstract":"<p><p>Interbacterial antagonism involves all major phyla, occurs across the full range of ecological niches, and has great significance for the environment, clinical arena, and agricultural and industrial sectors. Though the earliest insight into interbacterial antagonism traces back to the discovery of antibiotics, a paradigm shift happened when it was learned that protein secretion systems (e.g., types VI and IV secretion systems) deliver toxic \"effectors\" against competitors. However, a link between interbacterial antagonism and the Gram-negative type II secretion system (T2SS), which exists in many pathogens and environmental species, is not evident in prior reviews on bacterial competition or T2SS function. A current examination of the literature revealed four examples of a T2SS or one of its known substrates having a bactericidal activity against a Gram-positive target or another Gram-negative. When further studied, the T2SS effectors proved to be peptidases that target the peptidoglycan of the competitor. There are also reports of various bacteriolytic enzymes occurring in the culture supernatants of some other Gram-negative species, and a link between these bactericidal activities and T2SS is suggested. Thus, a T2SS can be a mediator of interbacterial antagonism, and it is possible that many T2SSs have antibacterial outputs. Yet, at present, the T2SS remains relatively understudied for its role in interbacterial competition. Arguably, there is a need to analyze the T2SSs of a broader range of species for their role in interbacterial antagonism. Such investigation offers, among other things, a possible pathway toward developing new antimicrobials for treating disease.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558705","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":"Role of cold shock proteins B and D in <i>Aeromonas salmonicida</i> subsp. <i>salmonicida</i> physiology and virulence in lumpfish (<i>Cyclopterus lumpus</i>).","authors":"Ahmed Hossain, Hajarooba Gnanagobal, Trung Cao, Setu Chakraborty, Joy Chukwu-Osazuwa, Manuel Soto-Dávila, Ignacio Vasquez, Javier Santander","doi":"10.1128/iai.00011-24","DOIUrl":"10.1128/iai.00011-24","url":null,"abstract":"<p><p>Cold shock proteins (Csp) are pivotal nucleic acid binding proteins known for their crucial roles in the physiology and virulence of various bacterial pathogens affecting plant, insect, and mammalian hosts. However, their significance in bacterial pathogens of teleost fish remains unexplored. <i>Aeromonas salmonicida</i> subsp. <i>salmonicida</i> (hereafter <i>A. salmonicida</i>) is a psychrotrophic pathogen and the causative agent of furunculosis in marine and freshwater fish. Four <i>csp</i> genes (<i>cspB, cspD, cspA</i>, and <i>cspC</i>) have been identified in the genome of <i>A. salmonicida</i> J223 (wild type). Here, we evaluated the role of DNA binding proteins, CspB and CspD, in <i>A. salmonicida</i> physiology and virulence in lumpfish (<i>Cyclopterus lumpus</i>). <i>A. salmonicida</i> Δ<i>cspB</i>, Δ<i>cspD</i>, and the double Δ<i>cspB</i>Δ<i>cspD</i> mutants were constructed and characterized. <i>A. salmonicida</i> Δ<i>cspB</i> and Δ<i>cspB</i>Δ<i>cspD</i> mutants showed a faster growth at 28°C, and reduced virulence in lumpfish. <i>A. salmonicida</i> Δ<i>cspD</i> showed a slower growth at 28°C, biofilm formation, lower survival in low temperatures and freezing conditions (-20°C, 0°C, and 4°C), deficient in lipopolysaccharide synthesis, and low virulence in lumpfish. Additionally, Δ<i>cspB</i>Δ<i>cspD</i> mutants showed less survival in the presence of bile compared to the wild type. Transcriptome analysis revealed that 200, 37, and 921 genes were differentially expressed in Δ<i>cspB</i>, Δ<i>cspD</i>, and Δ<i>cspB</i>Δ<i>cspD,</i> respectively. In Δ<i>cspB</i> and Δ<i>cspB</i>Δ<i>cspD</i> virulence genes in the chromosome and virulence plasmid were downregulated. Our analysis indicates that CspB and CspD mostly act as a transcriptional activator, influencing cell division (e.g., <i>treB</i>), virulence factors (e.g., <i>aexT</i>), and ultimately virulence.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450419","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":"Adherence and metal-ion acquisition gene expression increases during infection with <i>Treponema phagedenis</i> strains from bovine digital dermatitis.","authors":"Colton Scott, Angelica P Dias, Jeroen De Buck","doi":"10.1128/iai.00117-24","DOIUrl":"10.1128/iai.00117-24","url":null,"abstract":"<p><p>Digital dermatitis (DD) is an ulcerative foot lesion on the heel bulbs of dairy cattle. DD is a polymicrobial disease with no precise etiology, although <i>Treponema</i> spirochetes are found disproportionally abundant in diseased tissue. Within <i>Treponema,</i> several different species are found in DD; however, the species <i>Treponema phagedenis</i> is uniformly found in copious quantities and deep within the skin layers of the active, ulcerative stages of disease. The pathogenic mechanisms these bacteria use to persist in the skin and the precise role they play in the pathology of DD are widely unknown. To explore the pathogenesis and virulence of <i>Treponema phagedenis</i>, newly isolated strains of this species were investigated in a subcutaneous murine abscess model. In the first trial, a dosage study was conducted to compare the pathogenicity of different strains across three different treponemes per inoculum (TPI) doses based on abscess volumes. In the second trial, the expression levels of 11 putative virulence genes were obtained to gain insight into their involvement in pathogenesis. During the RT-qPCR analysis, it was determined that genes encoding for two metal-ion import lipoproteins and two adherence genes were found highly upregulated during infection. Conversely, two genes involved in motility and chemotaxis were found to not be significantly upregulated or utilized during infection. These results were supported by gene expression data from natural M2 lesions of dairy cattle. This gene expression analysis could highlight the preference in strategy for <i>T. phagedenis</i> to persist and adhere in the host rather than engage in motility and disseminate.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467729","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":"Taurine modulates host cell responses to <i>Helicobacter pylori</i> VacA toxin.","authors":"Mandy D Westland, Alexandra C Schrimpe-Rutledge, Simona G Codreanu, Stacy D Sherrod, John A McLean, Mark S McClain, Timothy L Cover","doi":"10.1128/iai.00224-24","DOIUrl":"10.1128/iai.00224-24","url":null,"abstract":"<p><p>Colonization of the human stomach with <i>Helicobacter pylori</i> strains producing active forms of the secreted toxin VacA is associated with an increased risk of peptic ulcer disease and gastric cancer, compared with colonization with strains producing hypoactive forms of VacA. Previous studies have shown that active s1m1 forms of VacA cause cell vacuolation and mitochondrial dysfunction. In this study, we sought to define the cellular metabolic consequences of VacA intoxication. Untargeted metabolomic analyses revealed that several hundred metabolites were significantly altered in VacA-treated gastroduodenal cells (AGS and AZ-521) compared with control cells. Pathway analysis suggested that VacA caused alterations in taurine and hypotaurine metabolism. Treatment of cells with the purified active s1m1 form of VacA, but not hypoactive s2m1 or Δ6-27 VacA-mutant proteins (defective in membrane channel formation), caused reductions in intracellular taurine and hypotaurine concentrations. Supplementation of the tissue culture medium with taurine or hypotaurine protected AZ-521 cells against VacA-induced cell death. Untargeted global metabolomics of VacA-treated AZ-521 cells or AGS cells in the presence or absence of extracellular taurine showed that taurine was the main intracellular metabolite significantly altered by extracellular taurine supplementation. These results indicate that VacA causes alterations in cellular taurine metabolism and that repletion of taurine is sufficient to attenuate VacA-induced cell death. We discuss these results in the context of previous literature showing the important role of taurine in cell physiology and the pathophysiology or treatment of multiple pathologic conditions, including gastric ulcers, cardiovascular disease, malignancy, inflammatory diseases, and other aging-related disorders.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554668","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":"Co-infection dynamics of <i>B. afzelii</i> and TBEV in C3H mice: insights and implications for future research.","authors":"Stefania Porcelli, Aurélie Heckmann, Pierre Lucien Deshuillers, Alejandra Wu-Chuang, Cleménce Galon, Lourdes Mateos-Hernandez, Sabine Rakotobe, Laetitia Canini, Ryan O M Rego, Ladislav Simo, Anne-Claire Lagrée, Alejandro Cabezas-Cruz, Sara Moutailler","doi":"10.1128/iai.00249-24","DOIUrl":"10.1128/iai.00249-24","url":null,"abstract":"<p><p>Ticks are important vectors of disease, particularly in the context of One Health, where tick-borne diseases (TBDs) are increasingly prevalent worldwide. TBDs often involve co-infections, where multiple pathogens co-exist in a single host. Patients with chronic Lyme disease often have co-infections with other bacteria or parasites. This study aimed to create a co-infection model with <i>Borrelia afzelii</i> and tick-borne encephalitis virus (TBEV) in C3H mice and to evaluate symptoms, mortality, and pathogen level compared to single infections. Successful co-infection of C3H mice with <i>B. afzelii</i> and TBEV was achieved. Outcomes varied, depending on the timing of infection. When TBEV infection followed <i>B. afzelii</i> infection by 9 days, TBEV symptoms worsened and virus levels increased. Conversely, mice infected 21 days apart with TBEV showed milder symptoms and lower mortality. Simultaneous infection resulted in mild symptoms and no deaths. However, our model did not effectively infect ticks with TBEV, possibly due to suboptimal dosing, highlighting the challenges of replicating natural conditions. Understanding the consequences of co-infection is crucial, given the increasing prevalence of TBD. Co-infected individuals may experience exacerbated symptoms, highlighting the need for a comprehensive understanding through refined animal models. This study advances knowledge of TBD and highlights the importance of exploring co-infection dynamics in host-pathogen interactions.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579566","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":"Substitutions in the nonactive site of the passenger domain on the activity of <i>Haemophilus influenzae</i> immunoglobulin A1 protease.","authors":"Chi-Wei Chen, Cheng-Hsun Ho","doi":"10.1128/iai.00193-24","DOIUrl":"10.1128/iai.00193-24","url":null,"abstract":"<p><p>Immunoglobulin A1 (IgA1) protease is a critical virulence factor of <i>Haemophilus influenzae</i> that facilitates bacterial mucosal infection. This study investigates the effect of <i>iga</i> gene polymorphism on the enzymatic activity of <i>H. influenzae</i> IgA1 protease. The IgA1 protease activity was examined in the <i>H. influenzae</i> Rd KW20 strain and 51 isolates. Genetic variations in <i>iga</i> and deduced amino acid substitutions affecting IgA1 protease activity were assessed. Machine learning tools and functional complementation assays were used to analyze the effects of identified substitutions on the stability and activity of IgA1 protease, respectively. All 51 isolates exhibited similar <i>iga</i> expression levels. No <i>igaB</i> expression was detected. According to comparisons with the reference Rd KW20 strain, four substitutions in the protease domain, 26 in the nonprotease passenger domain, and two in the β-barrel domain were associated with the change in IgA1 protease activity. No substitutions in the catalytic site of IgA1 protease were observed. Logistic regression, receiver operating characteristic curves, Venn diagrams, and protein stability analyses revealed that the substitutions Asn352Lys, Pro353Ala, Lys356Asn, Gln916Lys, and Gly917Ser, which were located in the nonactive site of the passenger domain, were associated with decreases in IgA1 protease activity and stability, whereas Asn914Lys was associated with an increase in these events. Functional complementation assays revealed that the Asn914Lys substitution increased IgA1 protease activity in the Rd KW20 strain. This study identified substitutions in the nonactive site of the passenger domain that affect both the activity and stability of <i>H. influenzae</i> IgA1 protease.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579567","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":"Immunization with an mRNA DTP vaccine protects against pertussis in rats.","authors":"Graham J Bitzer, Nicholas A Fitzgerald, Megan A DeJong, Casey Cunningham, Joshua A Chapman, Dylan T Boehm, Gage M Pyles, Annalisa B Huckaby, Sarah J Miller, Spencer R Dublin, Matthew D Warden, Mariette Barbier, F Heath Damron","doi":"10.1128/iai.00520-23","DOIUrl":"10.1128/iai.00520-23","url":null,"abstract":"<p><p><i>Bordetella pertussis</i> is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization <i>in vivo</i>. We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol <i>B. pertussis</i> challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized <i>B. pertussis</i> challenge in Sprague-Dawley rats.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626678","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}