Infection and Immunity最新文献

{"title":"Modeling chronic infection with <i>Mycoplasma pneumoniae</i> at an air-liquid interface: global transcriptional response of HBEC3-KT respiratory epithelial cells to biofilm towers.","authors":"Rasha A Fahim, Brynn G Cole, Jessica E Holland, Vanessa B Polster, Mitchell F Balish","doi":"10.1128/iai.00137-26","DOIUrl":"10.1128/iai.00137-26","url":null,"abstract":"<p><p><i>Mycoplasma pneumoniae</i>, a bacterial pathogen that causes chronic respiratory infections, grows as biofilm towers in both axenic culture and submerged tissue culture model systems. In these towers, virulence factor production is reduced. The clinical relevance of these towers is unclear because biofilms have not been examined in air-liquid interface (ALI) models of <i>M. pneumoniae</i> infection. We used differentiated HBEC3-KT human bronchial epithelial cells at an ALI to understand how <i>M. pneumoniae</i> grows on and interacts with airway cells in a more physiologically relevant setting than submerged systems, and to characterize the global transcriptional response of host cells in this context. We used scanning electron microscopy to examine the growth of <i>M. pneumoniae</i> on HBEC3-KT cells over time, employing a modified protocol to preserve mucus. This protocol revealed abundant biofilm towers associated with both ciliary tips and the mucus layer. RNA-seq analysis of HBEC3-KT cells at days 1 and 7 after infection indicated an early tempered cytokine response, followed later by induction of type III interferon, which is unexpected not only because that response is more typical of viruses, but also because <i>M. pneumoniae</i> is not known to enter host cells at an ALI. We assessed barrier function using transepithelial electrical resistance and culture of medium from the basal side of the host cells, revealing that disruption occurred, but only after prolonged infection. These results collectively suggest that <i>M. pneumoniae</i> limits damage to host cells when growing as biofilm towers by provoking only a selective inflammatory response, promoting chronic infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0013726"},"PeriodicalIF":3.4,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929045","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":"Interplay between proteostasis pathways and innate immune responses in <i>Caenorhabditis elegans</i>.","authors":"Annesha Ghosh, Jogender Singh","doi":"10.1128/iai.00037-26","DOIUrl":"10.1128/iai.00037-26","url":null,"abstract":"<p><p>Microbial pathogens frequently manipulate host protein homeostasis to undermine immunity by targeting protein synthesis, folding, trafficking, and degradation. Conversely, effective immune responses themselves impose substantial proteostatic demands, as the rapid production of antimicrobial effectors increases the burden on cellular quality-control systems. This bidirectional pressure has likely driven the evolution of surveillance mechanisms that sense disruptions in protein homeostasis as indicators of infection. Using <i>Caenorhabditis elegans</i> as a genetically tractable model, recent studies have revealed that perturbations in proteostasis across multiple cellular compartments, including the cytosol, endoplasmic reticulum (ER), mitochondria, proteasome, and extracellular space, are actively integrated with innate immune signaling. Stress-response pathways such as the heat shock response, translational regulation, and the unfolded protein responses of the ER and mitochondria function not only to restore proteome integrity but also to directly shape immune gene expression and pathogen resistance in a context-dependent manner. This review highlights proteostasis as an evolutionarily conserved immune surveillance system, linking cellular stress sensing to host defense and offering broader insights into the coupling of stress adaptation, immunity, and organismal health.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0003726"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770417","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":"Immune evasion by a chytrid fungus includes inhibition of macrophage phagocytosis.","authors":"Louise A Rollins-Smith, Mitchell Le Sage, Chelsea Roach Simoneau, Somya Singh, Muhammad Riadul Haque Hossainey, Carlos Henrique Serezani, Leon Grayfer","doi":"10.1128/iai.00591-25","DOIUrl":"10.1128/iai.00591-25","url":null,"abstract":"<p><p><i>Batrachochytrium dendrobatidis</i> continues to cause declines in amphibian populations worldwide, and it remains unclear why skin defenses often fail to control the infection. Although amphibians have a complex, multifunctional immune system, the chytridiomycosis agent seems to have evolved countermeasures that enable it to survive and eventually impair critical skin functions. Previous studies show that <i>B. dendrobatidis</i> cells or cell-free supernatants inhibit lymphocytes by inducing apoptosis, suggesting impaired local cell killing. However, there is little evidence of lymphocyte recruitment to chytrid-infected skin, implying the fungus may also inhibit the functions of antigen-presenting cells. Here, we demonstrate that phagocytosis by peritoneal macrophages is significantly reduced by co-culture with live or heat-killed <i>B. dendrobatidis</i> zoosporangia, freeze-thawed zoospores, fungal cell-free supernatants, or cell-wall fragments. The phagocytic capacity of frog bone marrow-derived macrophages, differentiated by colony-stimulating factor-1 (CSF-1) or interleukin-34 (IL-34) (key macrophage growth factors), as well as immortalized mammalian macrophages, is also impaired. Inhibition of mammalian macrophages suggests that these inhibitory factors are not restricted to amphibian cells. Overall, these studies indicate that <i>B. dendrobatidis</i> cells and their components can hinder the recognition and function of macrophages that reside in or enter the skin to clear infections. This disabling of host phagocytosis is undoubtedly central to how <i>B. dendrobatidis</i> prevents effective innate and adaptive immune responses in the skin.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0059125"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581291","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":"Construction and characterization of novel <i>Mycobacterium tuberculosis</i>-derived triple and quadruple knockout vaccines against tuberculosis.","authors":"Omar Garnica, Raja Veerapandian, Kishore Das, Abhishek Mishra, Varsha Rawat, Areanna Carmona, Vivek Chauhan, Rakesh Kumar, Jessica Chacon, Arshad Khan, Enrique I Ramos, Shrikanth S Gadad, Chinnaswamy Jagannath, Subramanian Dhandayuthapani","doi":"10.1128/iai.00500-25","DOIUrl":"10.1128/iai.00500-25","url":null,"abstract":"<p><p>Tuberculosis (TB) is a deadly disease that claims the lives of over a million people each year worldwide. The Bacille Calmette-Guérin vaccine has long been used to protect against TB, but it produces variable effects across different populations and fails to protect against adult pulmonary TB. Therefore, there is an urgent need for alternative vaccines that can offer better protection. We have developed a strategy for the rational deletion of virulence-related genes in <i>Mycobacterium tuberculosis</i> (Mtb) to create hyperattenuation that also enhances immunogenicity. Previously, we generated both single (<i>∆fbpA</i>) and double knockout (DKO) (<i>∆fbpA-∆sapM</i>) mutants of Mtb and assessed their immunogenicity and efficacy using mice. Herein, we have created triple knockout (TKO) and quadruple knockout (QKO) strains to enhance the immunogenicity and safety of the DKO strain by deleting the <i>zmp1</i> and <i>dosR</i> genes. The resulting TKO strains, TKO-Z (<i>∆fbpA-∆sapM-∆zmp1</i>) and TKO-D (<i>∆fbpA-∆sapM-∆dosR</i>), and the QKO strain (<i>∆fbpA-∆sapM-∆zmp1-∆dosR</i>), were evaluated for their immunogenicity and safety in mice. Whereas TKO-Z and QKO strains exhibited superior immunogenicity compared to the DKO strain, their protective efficacy in mice was comparable. However, survival studies involving SCID mice indicated that the QKO strain was highly attenuated. Therefore, rational deletion of genes in Mtb seems to be an innovative approach for developing safer and more efficacious vaccines against TB.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0050025"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770442","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":"Comparison of macrophage responses between high- and low-virulent strain <i>Edwardsiella tarda</i> infections in mouse macrophage RAW264.7 cells: interleukin-1β secretion as a key macrophage response to a high-virulent strain <i>E. tarda</i>.","authors":"Xiao-Mi Sun, Mikinori Ueno, Hirofumi Tamaru, Katsuya Hirasaka, Tatsuya Oda, Asami Yoshida, Kiyoshi Osatomi","doi":"10.1128/iai.00663-25","DOIUrl":"10.1128/iai.00663-25","url":null,"abstract":"<p><p><i>Edwardsiella tarda,</i> a major facultative intracellular pathogen affecting aquaculture, can cause hemorrhagic septicemia and hemolytic ascites disease in aquaculture fish. It is characterized by the ability to survive and replicate in macrophages. In this study, mouse macrophage cell line RAW264.7 cells were used as a model system to study macrophage responses toward <i>E. tarda in vitro</i>. We found that the high-virulent strain NUF251 can survive and multiply in RAW264.7 cells, but the low-virulent strain NUF194 has no such ability. These results were consistent with our previous study conducted in fish macrophages. Both strains induced an increase in intracellular reactive oxygen species and secretion of nitric oxide and tumor necrosis factor-α in RAW264.7 cells, but significantly higher levels of these mediators were induced by NUF194. In addition, DNA fragmentation concomitant with slight activation of caspase-3 was observed in NUF194-infected RAW264.7 cells, suggesting the occurrence of apoptosis, whereas no such clear typical apoptosis symptoms were detected in NUF251-infected RAW264.7 cells. Interestingly, a much higher level of interleukin (IL)-1β was secreted from NUF251-infected RAW264.7 cells as compared to those of NUF194-infected or LPS-treated cells, especially at 3 h post-infection, even though similar levels of IL-1β mRNA were detected in all these cells. Since the secretion of IL-1β is a characteristic feature of pyroptosis, our results suggest that induction of pyroptosis accompanied by IL-1β secretion may be a specific macrophage response linked with the virulence of <i>E. tarda</i> infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0066325"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770289","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":"Lipidated Protein D vaccination elicits humoral and cellular responses and protects mice against challenge with non-typeable <i>Haemophilus influenzae</i>.","authors":"Terri C Thayer, Andrew Cox, Eduardo Gonzalez, Jill Mangiafesto, Lei Xu, Michael Pichichero, Ravinder Kaur","doi":"10.1128/iai.00647-25","DOIUrl":"10.1128/iai.00647-25","url":null,"abstract":"<p><p>Nontypeable <i>Haemophilus influenzae</i> (<i>NTHi</i>) is a primary cause of acute otitis media (AOM) in children and lower respiratory tract infections in adults. Vaccines that can reduce nasopharyngeal carriage and prevent disease are needed. We used an adult murine model of nasopharyngeal carriage and AOM infection to evaluate immunogenicity and protection provided by subcutaneous and intramuscular vaccination with lipidated Protein D (L-PD) compared with non-lipidated PD (NL-PD) formulated with and without alum adjuvant. ELISA was used for antibody measurements and flow cytometry to characterize T-cell immunity. L-PD + Alum subcutaneous vaccination induced low levels of PD-specific IgG antibodies and significantly elevated Th17 and T effector memory cell activation in cervical lymph nodes and splenocytes compared with NL-PD + Alum. The addition of alum increased bactericidal antibody activity. Intramuscular vaccination with L-PD with and without alum induced 3- to 4-fold log₁₀ higher PD-specific IgG antibodies than subcutaneous vaccination but did not elicit Th17 or T effector memory cell activation. Subcutaneous vaccination with L-PD + Alum protected mice within both the nasopharynx and middle ear. Middle ear bacterial density reduction correlated with IgG antibody levels after intramuscular vaccination with L-PD + Alum but not L-PD without alum, yet no protection from nasopharyngeal carriage occurred. PD + Alum vaccination increased humoral and cellular immunity and protected mice from <i>NTHi</i> carriage and AOM, whereas NL-PD did not. Activation of Th17 immunity by lipidation of PD and subcutaneous vaccination correlated with protection from nasopharyngeal carriage of <i>NTHi</i>.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0064725"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581244","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":"Aspartate aminotransferase is required for <i>Salmonella</i> expansion in the inflamed gut via TCA anaplerosis.","authors":"N G Shealy, M Baltagulov, H F Avalos, J Olivas, K M Jones, M X Byndloss","doi":"10.1128/iai.00161-26","DOIUrl":"10.1128/iai.00161-26","url":null,"abstract":"<p><p>Aspartate represents an important proteogenic amino acid in all living organisms. Many microorganisms can produce aspartate through various biosynthetic processes, utilizing it for energy production and as a precursor for synthesizing other biomolecules, such as amino acids and nucleotides. The enteric pathogen <i>Salmonella enterica</i> serovar Typhimurium (<i>S</i>. Tm) has developed mechanisms to access aspartate as a nutrient source during expansion in the inflamed gut. However, how <i>S</i>. Tm deals with aspartate starvation during infection remains unknown. To address this knowledge gap, we interrogated <i>Salmonella</i>'s reliance on the bidirectional aspartate aminotransferase encoded by <i>aspC</i> for growth <i>in vitro</i> and during host colonization using murine models of <i>Salmonella</i> infection. AspC can interconvert aspartate and the TCA intermediate oxaloacetate and is hypothesized to support <i>S</i>. Tm cellular demands for aspartate during starvation or support refueling of the TCA cycle via oxaloacetate synthesis. Herein, we find that loss of <i>aspC</i> results in a gut-specific <i>S</i>. Tm colonization defect that increases with the course of infection. Importantly, <i>aspC</i> is dispensable for <i>S</i>. Tm systemic colonization in CBA/J mice. Additionally, we report that loss of <i>aspC</i> results in a significant growth defect during respiration of inflammation-derived electron acceptors <i>in vitro</i>. Interruption of oxidative TCA cycle progression via TCA enzyme deletion or supplementation with TCA intermediates (e.g., oxaloacetate) abrogates the defect observed in Δ<i>aspC S</i>. Tm <i>in vitro</i>, thus suggesting the requirement for AspC to catabolize aspartate and support the TCA cycle during respiration. Altogether, we report that AspC plays a critical role in <i>S</i>. Tm pathogenesis in a gut-specific manner during inflammation through supporting energy generation.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0016126"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573953","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":"Nicotinamide attenuates the virulence of colorectal cancer-associated <i>Fusobacterium nucleatum</i>.","authors":"Ziyi Yang, Zixue Lei, Qizhao Ma, Jumei Zeng, Mai Xu, Dian Zhang, Pei Xu, Kai Li, Tao Gong, Yuqing Li","doi":"10.1128/iai.00488-25","DOIUrl":"10.1128/iai.00488-25","url":null,"abstract":"<p><p><i>Fusobacterium nucleatum</i> contributes to the progression of colorectal cancer (CRC). Nicotinamide (NAM), a safe, cost-effective, and water-soluble form of vitamin B3, has been shown to inhibit the virulence of various microorganisms. However, its effect on <i>F. nucleatum</i> pathogenicity remains unclear. In this study, we evaluated the effects of NAM on the pathogenic traits of <i>F. nucleatum</i>. A quarter of the minimum inhibitory concentration of NAM (~50 mM) was found to simultaneously inhibit bacterial growth, biofilm formation, and the adhesion and invasion of CRC cells. Transcriptomic analysis of <i>F. nucleatum</i> treated at this concentration revealed that 257 genes were upregulated and 316 genes were downregulated. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology functional enrichment analyses indicated that these differentially expressed genes are involved in multiple pathways, including oxidative phosphorylation, biofilm formation, two-component systems, ATP synthesis, and other processes. Furthermore, we showed that NAM, as a class III histone deacetylase inhibitor, could inhibit the deacetylase activity of CobB, thereby increasing the acetylation level of the FomA and reducing its binding ability to CRC cells. In summary, these findings suggest that NAM can attenuate multiple virulence traits of <i>F. nucleatum</i> and may serve as a promising <i>F. nucleatum-</i>targeted strategy for prevention and treatment of CRC.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0048825"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573899","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":"Endogenous cathelicidin protects against <i>Toxoplasma gondii-</i>associated liver damage.","authors":"Yi Lin Tan, Paloma Cavalcante, Karina M Cirone, Jacquelyn Tran, Franco Fiorani, Daniel Young, Antoine Dufour, Constance Finney, Eduardo R Cobo","doi":"10.1128/iai.00708-25","DOIUrl":"10.1128/iai.00708-25","url":null,"abstract":"<p><p>Toxoplasmosis, a disease caused by apicomplexan <i>Toxoplasma gondii (Tg)</i>, is associated with various neuropsychiatric and behavioral conditions. Toxoplasmosis can cause serious complications for those with weakened immune systems and during pregnancy. Cathelicidins, peptides with antimicrobial and immunomodulatory functions, are critical factors in host defense against microbes, but their role in parasitic infections is less well understood. This study demonstrates the protective function of endogenous cathelicidin against hepatic damage caused by <i>Tg</i> infection in an oral infection model. We challenged wild-type (<i>Camp^+/+</i>) and cathelicidin-deficient (<i>Camp^-/-</i>) mice with low-virulent Type II strain of <i>Tg</i> (ME-49) cysts. Our findings demonstrate that <i>Camp^-/-</i> mice exhibited more severe clinical manifestations, higher mortality rates, and more pronounced hepatic damage compared to their <i>Camp^+/+</i> counterparts. Histological liver examinations indicated significant necrotic hepatitis in <i>Camp^-/-</i> mice, correlating with increased local concentrations of pro-inflammatory cytokines and proteomic upregulation of poly(ADP-ribose) polymerase 3 and guanylate-binding proteins. Increased cerebral inflammation and <i>Tg</i> cystogenesis were also observed in <i>Camp^-/-</i> mice. Systemically, <i>Camp^-/-</i> mice presented elevated levels of pro-inflammatory mediators, specifically interferon-gamma (Ifn-γ) and tumor necrosis factor-alpha (Tnf-α). In cultured macrophages, endogenous cathelicidin increased after <i>Tg</i> challenge, while <i>Camp^-/-</i> bone marrow-derived macrophages released higher amounts of Tnf-α than their counterparts. We conclude that cathelicidin protects against liver injury and systemic deterioration induced by <i>Tg</i> infection by downregulating the synthesis of pro-inflammatory cytokines.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0070825"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270826","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":"OspA antibodies inhibit the <i>in vitro</i> transmigration of <i>Borrelia burgdorferi</i>.","authors":"Ankita Bhattacharyya, Nicholas J Mantis","doi":"10.1128/iai.00128-26","DOIUrl":"10.1128/iai.00128-26","url":null,"abstract":"<p><p>Antibodies against Outer surface protein A (OspA) block tick-to-mammal transmission of the Lyme disease spirochete, <i>Borrelia burgdorferi</i>. Evidence suggests that antibodies ingested by a tick during a blood meal entrap OspA-expressing <i>B. burgdorferi</i> within the tick midgut and prevent spirochete migration to the salivary gland and host dermis. In this study, we employed a recently described Transwell system to quantitate the impact of OspA antibodies on <i>B. burgdorferi</i> transmigration. We demonstrate that spirochete movement from the lower Transwell chamber to the upper chamber over a 20-h period was reduced by <u>></u>99% in the presence of the transmission-blocking mouse monoclonal IgG antibody (mAb) LA-2. In the case of LA-2, transmigration inhibition coincided with the formation of large antibody-induced bacterial aggregates in the lower Transwell chamber, as determined by dark field microscopy and flow cytometry. Further examination of a panel of human OspA mAbs of varying affinities and epitope specificities revealed that virtually all could block <i>B. burgdorferi</i> transmigration although most did so in the absence of measurable spirochete agglutination. We propose that transmigration arrest may represent a possible mechanism by which OspA antibodies entrap <i>B. burgdorferi</i> in the tick midgut and limit transmission to mammalian hosts.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0012826"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770399","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}