Pathogens and Immunity最新文献

{"title":"Diagnostic Certainty in Registry-Based Estimates of Innate and Intrinsic Immunity Defects.","authors":"Nezihe Köker Özer, Ercan Yılmaz, Erdem Topal","doi":"10.20411/pai.v11i2.1108","DOIUrl":"10.20411/pai.v11i2.1108","url":null,"abstract":"","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 2","pages":"127-129"},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Historical Highlight: Three Seminal Articles Relating to the Recognition of Protein Antigens by Antibodies.","authors":"Neil S Greenspan, Emily N Kukan","doi":"10.20411/pai.v11i2.1091","DOIUrl":"https://doi.org/10.20411/pai.v11i2.1091","url":null,"abstract":"","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 2","pages":"116-126"},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Evaluation of Administered FITC-Dextran or Evans Blue Dye to Determine Intestinal Barrier Permeability in Nonhuman Primates.","authors":"Elizabeth G Bodykevich, Carol L Vinton, Alexandra M Ortiz, Jason M Brenchley","doi":"10.20411/pai.v11i2.1054","DOIUrl":"10.20411/pai.v11i2.1054","url":null,"abstract":"<p><strong>Background: </strong>Microbial translocation is a key contributor to chronic immune activation during HIV infection. Current methods of measuring microbial translocation are limited in sensitivity and are largely indirect, underscoring the need for more precise and direct techniques that can be followed longitudinally. We aimed to address this gap by applying modalities commonly employed in mouse models of intestinal permeability.</p><p><strong>Methods: </strong>We explored whether oral FITC-Dextran or suppository-delivered Evans blue dye in nonhuman primates could be leveraged to approximate intestinal barrier disruption in healthy and SIV-infected rhesus macaques.</p><p><strong>Results: </strong>After administration, FITC-Dextran was detected at comparable concentrations in the plasma of healthy and chronically infected animals, whereas healthy animals had greater concentrations of Evans blue dye as compared to chronically infected animals. Evans blue was reliably detected in phagocytic cells across tissue types, with detection often highest in the rectum, liver, and spleen biopsies. Exogenous uracil modulated an increase in intestinal barrier permeability observed through standard markers, which was not reliably reflected on Evans blue uptake.</p><p><strong>Conclusion: </strong>These data demonstrate that dye-based measurements of intestinal permeability routinely used in murine models are not sufficient in nonhuman primates, and that common biomarkers and/or sugar permeability and immunohistochemical approaches are still preferred.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 2","pages":"96-115"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of Airborne Virus Transmission in the Built Environment: A Narrative Review.","authors":"Yizhi Zhang, Kathryn C Krupinsky, Adam S Lauring, Linsey C Marr","doi":"10.20411/pai.v11i2.1049","DOIUrl":"10.20411/pai.v11i2.1049","url":null,"abstract":"<p><p>The COVID-19 pandemic accelerated recognition of airborne transmission of respiratory infections. Despite improved mechanistic understanding, our ability to predict the risk of infection in a given scenario remains limited, owing, in part, to high heterogeneity in factors involved in transmission. The goal of this work is to quantify variability in factors that control risk of airborne virus transmission in the built environment. Using SARS-CoV-2 as a model, we conducted a narrative review on transmission via inhalable respiratory particles (≤100 μm). We divided transmission into 3 key processes: emissions of virus in respiratory particles from an infected individual (the source) into the air; transport and decay of virus in the environment; and deposition and infection in a new host (the receiver). Among the source-related factors, we found large variabilities spanning 7 or more orders of magnitude. For example, the rate of respiratory emissions from an infected individual ranges from ~1 to > 10⁷ particles per second, depending in part on the type of respiratory activity and individual physiological factors. Unexplained inter-individual variations, such as those defining \"superemitters,\" introduce additional uncertainties. We also found considerable variability in the physical and biological decay of virus-laden particles as they move from the source to the receiver. The air exchange rate, which controls physical loss of particles by ventilation, ranges from ~0.01 to > 20 air changes per hour in typical buildings. Lastly, upon inhalation, the efficiency and site of virus deposition vary with the physiological state of the receiver, whose immunological status further influences whether infection is established. Overall, we found the largest variability in the rate of respiratory particle production and viral load of respiratory fluid. These 2 factors determine the amount of virus released into the air by an infected person, which is a critical indicator of the potential for onward transmission. Predicting the risk of infection in a specific scenario remains challenging due to the combined effects of variability in key determinants.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 2","pages":"66-95"},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keystone Epitope Theory: An Ecological Perspective on RNA Viruses, Tumor Immunoediting, and Vaccine Design.","authors":"Simon Mallal, Amir Asiaee","doi":"10.20411/pai.v11i2.1011","DOIUrl":"10.20411/pai.v11i2.1011","url":null,"abstract":"<p><p>We propose that persistent, human-adapted DNA organisms shape postnatal immunity by focusing responses on functionally constrained epitopes within tissue niches. Here, we examine rapidly evolving RNA viruses and tumors through that lens. We propose that their persistence is promoted by 2 coupled mechanisms: (i) immunodominance steering toward mutable \"decoy\" epitopes that contribute little to durable control, and (ii) antigen display control that reduces cytotoxic T lymphocyte (CTL) recognition while preserving inhibitory natural killer (NK) receptor engagement, for example via HIV Nef/Vpu effects on HLA-A and HLA-B and through HLA-E/NKG2A pathways. Tumors show analogous vulnerabilities through altered class I expression and reinforcement of inhibitory signaling. Using HIV as the primary model, we distinguish HLA-associated viral adaptation mechanisms and highlight evidence consistent with a subset of adaptations that preserve detectable T-cell recognition while being associated with reduced antiviral effector function. We then consider the degree to which this framework can be extended to hepatitis C virus (HCV), influenza, SARS-CoV-2, and tumor immunoediting. We conclude with 3 vaccine design principles: prioritize epitopes where substitutions carry measurable fitness costs, avoid immunogens dominated by mutable targets, and account for antigen presentation context and inhibitory NK signaling when evaluating epitope choice. We distinguish established observations from testable predictions and outline experiments needed to evaluate the framework. We frame the analysis conditionally on the keystone-imprinting premise, which is developed in companion work.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 2","pages":"39-65"},"PeriodicalIF":0.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keystone Epitope Theory: Implications for Hypersensitivity, Autoimmunity, and Transplantation.","authors":"Simon Mallal, Amir Asiaee, Elizabeth Phillips","doi":"10.20411/pai.v11i2.1016","DOIUrl":"https://doi.org/10.20411/pai.v11i2.1016","url":null,"abstract":"<p><p>HLA class I alleles confer a striking risk for T cell-mediated drug hypersensitivity, yet positive predictive values are low-typically under 10% and as low as 0.12% for some drug-HLA pairs. We propose that persistent, human-adapted pathogens-notably herpesviruses-focus postnatal immune memory on conserved epitopes in the tissue niches where viral control occurs (the Keystone Epitope Theory). The phylogenetic basis for this proposal is that herpesviruses and their vertebrate hosts have co-adapted over hundreds of millions of years, and that this co-evolutionary relationship is replayed ontogenetically as each individual acquires these infections and builds tissue-specific immune memory. When a drug-altered self-peptide approximates the geometry of such a target and is presented by the same risk HLA in the same niche at sufficient density, pre-existing tissue-resident memory T cells (TRM) may be recruited, breaching local regulatory equilibria and driving immunopathology. We synthesize three strands of evidence: (i) heterologous immunity, in which virus-imprinted TRM cross-recognize drug-modified self; (ii) antigen presentation in the same tissue where antiviral memory already resides, which helps explain why injury is tissue-restricted; and (iii) public and private TCR solutions that bridge viral and self-targets. Beginning with T cell-mediated drug hypersensitivity as an empirical anchor, we extend this framework to EBV-associated multiple sclerosis and transplant rejection and conclude with proposed experimental validation strategies that may be applicable more broadly to T cell-mediated hypersensitivity and autoimmunity.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 2","pages":"16-38"},"PeriodicalIF":0.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mast Cells Control the Bacterial Burden and Grain Formation in Murine Experimental Actinomycetoma Induced by <i>Nocardia brasiliensis</i>.","authors":"Tomás Alejandro Suárez-Vázquez, Nallely López-López, Manuel Mejía-Torres, Adrián G Rosas-Taraco, Raquel Garza-Guajardo, Yatsiri G Meneses-Preza, Bibiana Patricia Ruiz-Sánchez, Rommel Chacón-Salinas, Mario César Salinas-Carmona","doi":"10.20411/pai.v11i2.1003","DOIUrl":"10.20411/pai.v11i2.1003","url":null,"abstract":"<p><strong>Background: </strong>The immunopathogenesis of actinomycetoma, a chronic granulomatous infection caused primarily by <i>Nocardia brasiliensis</i>, involves poorly defined mechanisms sustaining its characteristic cyclical inflammation.</p><p><strong>Methods: </strong>Using MCdeficient <i>Kit^W-sh/W-sh</i> mice, this study investigated the role of mast cells (MCs) in a murine model of actinomycetoma. Clinical progression, bacterial burden, histopathology, and lesional leukocyte infiltration were analyzed at 30 and 72 days postinfection, and bone marrowderived MCs were challenged <i>in vitro</i> with <i>Nocardia brasiliensis</i> to assess activation.</p><p><strong>Results: </strong>MC-deficient mice exhibited a significant increase in bacterial load concomitant with attenuated late-phase (72-day) inflammation, characterized by reduced lesional neutrophilia and lymphocytic infiltration. Furthermore, MC absence disrupted the characteristic morphology of bacterial grains. <i>In vitro, N. brasiliensis</i> induced potent MC degranulation and pro-inflammatory cytokine release.</p><p><strong>Conclusions: </strong>These data demonstrate that MCs are directly activated by <i>N. brasiliensis</i> and contribute to a delayed protective immune response, modulating late-stage inflammatory containment and bacterial clearance in experimental mycetoma.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 2","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NF-κB/OCT-1 Mediated Upregulation of CXCL14 Chemokine Mobilizes Mucosal Effector Memory CD44+CD62L-CD4+ and CD8+ TEM Cells, and NK Cells Associated with Protection Against Genital Herpes.","authors":"Yassir Lekbach, Swayam Prakash, Hawa Vahed, Afshana Quadiri, Azizur Rahman, El Houcine El Fatimi, Joshua Christian Dorotta, Baverly Sabathini Suoth, Chhaya Maurya, America Garcia, Gina Park, Lbachir BenMohamed","doi":"10.20411/pai.v11i1.879","DOIUrl":"10.20411/pai.v11i1.879","url":null,"abstract":"<p><strong>Background: </strong>Mucosal chemokines (eg, CCL25, CCL28, CXCL14, and CXCL17) play key roles in protecting mucosal surfaces against invading infectious pathogens. However, their specific contributions to protection against genital herpes remain to be fully elucidated. Here, we investigated the role of CXCL14 as a mediator of mucosal immunity against genital HSV-2 infection and disease.</p><p><strong>Methods: </strong><i>CXCL14</i> expression was analyzed in HSV-specific CD8⁺ T cells from HSV-2-infected asymptomatic and symptomatic women, in primary human vaginal epithelial cells, and in a murine genital HSV-2 infection model. <i>CXCL14(-/-)</i> deficient mice and wild-type (WT) mice were compared for genital disease severity, vaginal viral loads, survival, immune cell recruitment, and T-cell effector function following intravaginal HSV-2 infection. Chromatin immunoprecipitation assays were performed to identify transcription factors binding to the <i>CXCL14</i> promoter after HSV-2 infection.</p><p><strong>Results: </strong>CXCL14 was homeostatically expressed at the genital tract mucosal surface, and HSV-specific CD8⁺ T cells from HSV-2-infected asymptomatic women expressed significantly higher levels of CXCL14 than those from symptomatic women. HSV-2 infection rapidly induced <i>CXCL14</i> transcription and production in primary human vaginal epithelial cells and in murine vaginal mucocutaneous tissue. <i>CXCL14(-/-)</i> mice developed more severe genital lesions, higher vaginal viral loads, and lower survival compared to WT mice. In addition, <i>CXCL14</i> deficiency impaired the recruitment of natural killer (NK) cells, neutrophils, and CD44⁺CD62L^- effector memory CD4⁺ and CD8⁺ T cells to the infected vaginal mucosa. It reduced T cell effector functions, including production of IFN-γ, TNF-α, and Granzyme B. Mechanistically, NF-κB and OCT-1 transcription factors bound to the CXCL14 promoter within hours of HSV-2 infection.</p><p><strong>Conclusions: </strong>Our findings demonstrate that NF-κB- and OCT-1-driven CXCL14 expression is crucial for orchestrating early innate and T-cell responses that protect against genital HSV-2 infection and disease. These results suggest that CXCL14 is an important immunoregulatory chemokine triggered early after epithelial viral infection, facilitating the induction of effective mucosal protective immunity against genital herpes.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 1","pages":"191-222"},"PeriodicalIF":0.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Year in Review on Tuberculosis and Non-tuberculous Mycobacteria Disease: A 2026 Update for Clinicians and Scientists.","authors":"Simone Tunesi, Graham Bothamley, Gunar Günther, Yousra Kherabi, Liga Kuksa, Berit Lange, Christoph Lange, Natalie Lorent, Francesca Saluzzo, Martina Sester, Xenia Emilie Sinding Iversen, Marc Tebruegge, Conor Tweed, Anca Vasiliu, Lorenzo Guglielmetti","doi":"10.20411/pai.v11i1.970","DOIUrl":"10.20411/pai.v11i1.970","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide, while infections from non-tuberculous mycobacteria (NTM) represent a growing public health threat. In its 20^th year of activity, the Tuberculosis Network European Trials group (TBnet; www.tbnet.eu) is one of the leading research networks in Europe. In this review, we summarize the main advances in TB and NTM that occurred in 2025.</p><p><strong>Methods: </strong>We conducted a non-systematic review of articles published in 2025, with a strong emphasis on research with current or potential impact on clinical practice. We also selected the most impactful papers regarding the management of adult TB, pediatric TB, and NTM infections.</p><p><strong>Results: </strong>Members of the TBnet Steering Committee summarize the main advances in their areas of interest, including epidemiology, pathogenesis, prevention, diagnosis, treatment, pediatric TB, and NTM infections. We also include a summary of future research priorities.</p><p><strong>Conclusions: </strong>The year 2025 presented many exciting advancements in almost all fields of mycobacterial science. This article provides an expert-based, clinically orientated summary of the main new findings in the TB and NTM fields and aims to provide an updated overview of the state of the art in those areas.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 1","pages":"154-190"},"PeriodicalIF":0.0,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Sex on Viral Shedding and Symptom Severity During Acute COVID-19.","authors":"Evelyn Kung, Rinki Deo, Manish C Choudhary, Kara W Chew, Teresa H Evering, Rachel Bender Ignacio, Prasanna Jagannathan, James P Flynn, James Regan, Carlee Moser, Mark J Giganti, Michael D Hughes, Justin Ritz, Arzhang Cyrus Javan, Alexander L Greninger, Upinder Singh, William Fischer, Eric S Daar, David A Wohl, Joseph J Eron, Judith S Currier, Robert W Coombs, Davey M Smith, Jonathan Z Li","doi":"10.20411/pai.v11i1.971","DOIUrl":"10.20411/pai.v11i1.971","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the impact of sex on acute SARS-CoV-2 infection, 668 participants from the ACTIV-2/A5401 study were followed over a 28-day period.</p><p><strong>Methods: </strong>A primary analysis was performed on 469 participants with quantifiable viral loads at baseline.</p><p><strong>Results: </strong>Male and female participants had comparable nasal SARS-CoV-2 RNA levels at study entry and throughout follow-up. However, sex-specific differences in viral shedding emerged when stratified by symptom duration. In the first 3 days after symptom onset, female participants exhibited higher nasal SARS-CoV-2 RNA levels than males, but lower viral RNA levels thereafter. The higher viral RNA levels in females during the earliest phase of acute COVID-19 were observed even after adjusting for age, race, and region of enrollment. Female participants also tended to have higher symptom scores across days since symptom onset, but no significant correlation was observed between nasal SARS-CoV-2 RNA levels and symptom score regardless of sex.</p><p><strong>Conclusion: </strong>These findings highlight the impact of sex on both viral shedding and symptom dynamics and underscore the importance of considering time since symptom onset when evaluating antiviral therapies for respiratory viruses in clinical trials.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 1","pages":"142-153"},"PeriodicalIF":0.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147976097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}