Pathogens and Immunity最新文献

{"title":"The Odyssey of Lupus","authors":"Patrick Ashinze","doi":"10.20411/pai.v9i1.699","DOIUrl":"https://doi.org/10.20411/pai.v9i1.699","url":null,"abstract":"It begins with a blush,the kind that doesn’t vanish,even with sadnessor the hush of immune calmers. \u0000then, it upscalesinto a flash of lightning,stabbing the skies with boltsof redness and irritation,making the body a slow, feralpoison unto its own beauty\u0000until all the cells, all the pillars that hold the fortall zones and hopes are friedand the bored earth is forcedout of pity and derisionto eat cold dinner at breakfast.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"18 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140744820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: “The Chemical Characterization of the Pneumococcal Transforming Principle. Pathogens and Immunity. 2024;8(2):177–178. doi: 10.20411/pai.v8i2.687”","authors":"Neil S. Greenspan","doi":"10.20411/pai.v9i1.704","DOIUrl":"https://doi.org/10.20411/pai.v9i1.704","url":null,"abstract":"[This corrects the article DOI: 10.20411/pai.v8i2.687.].","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"253 ","pages":"18 - 18"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140751600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric Antigen Receptor (CAR)-T Cell Therapy for Non-Hodgkin’s Lymphoma","authors":"M. Giraudo, Zachary Jackson, Indrani Das, Olubukola Abiona, David Wald","doi":"10.20411/pai.v9i1.647","DOIUrl":"https://doi.org/10.20411/pai.v9i1.647","url":null,"abstract":"This review focuses on the use of chimeric antigen receptor (CAR)-T cell therapy to treat non-Hodgkin’s lymphoma (NHL), a classification of heterogeneous malignant neoplasms of the lymphoid tissue. Despite various conventional and multidrug chemotherapies, the poor prognosis for NHL patients remains and has prompted the utilization of groundbreaking personalized therapies such as CAR-T cells. CAR-T cells are T cells engineered to express a CAR that enables T cells to specifically lyse tumor cells with extracellular expression of a tumor antigen of choice. A CAR is composed of an extracellular antibody fragment or target protein binding domain that is conjugated to activating intracellular signaling motifs common to T cells. In general, CAR-T cell therapies for NHL are designed to recognize cellular markers ubiquitously expressed on B cells such as CD19+, CD20+, and CD22+. Clinical trials using CAR-T cells such as ZUMA-7 and TRANSFORM demonstrated promising results compared to standard of care and ultimately led to FDA approval for the treatment of relapsed/refractory NHL. Despite the success of CAR-T therapy for NHL, challenges include adverse side effects as well as extrinsic and intrinsic mechanisms of tumor resistance that lead to suboptimal outcomes. Overall, CAR-T cell therapies have improved clinical outcomes in NHL patients and generated optimism around their future applications.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"2 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140238825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?","authors":"Justin Harper, Michael R Betts, Mathias Lichterfeld, Michaela Müller-Trutwin, David Margolis, Katharine J Bar, Jonathan Z Li, Joseph M McCune, Sharon R Lewin, Deanna Kulpa, Santiago Ávila-Ríos, Dázon Dixon Diallo, Michael M Lederman, Mirko Paiardini","doi":"10.20411/pai.v8i2.696","DOIUrl":"10.20411/pai.v8i2.696","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.20411/pai.v8i2.665.].</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 2","pages":"179-222"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176882","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":"Time to Think Antifungal Resistance Increased Antifungal Resistance Exacerbates the Burden of Fungal Infections Including Resistant Dermatomycoses.","authors":"Thomas S McCormick, Mahmoud Ghannoum","doi":"10.20411/pai.v8i2.656","DOIUrl":"10.20411/pai.v8i2.656","url":null,"abstract":"<p><p>Increased antifungal resistance is exacerbating the burden of invasive fungal infections, as well as potentially contributing to the increase in resistant dermatomycoses. In this commentary, we focus on antifungal drug resistance, in contrast to antibacterial resistance. We provide a brief historical perspective on the emergence of antifungal resistance and propose measures for combating this growing health concern. The increase in the incidence of invasive and cutaneous fungal infections parallels advancements in medical interventions, such as immunosuppressive drugs, to manage cancer and reduce organ rejection following transplant. A disturbing relatively new trend in antifungal resistance is the observation of several fungal species that now exhibit multidrug resistance (eg, <i>Candida auris, Trichophyton indotineae</i>). Increasing awareness of these multidrug-resistant species is paramount. Therefore, increased education regarding potential fungus-associated infections is needed to address awareness in the general healthcare setting, which may result in a more realistic picture of the prevalence of antifungal-resistant infections. In addition to education, increased use of diagnostic tests (eg, micro and macro conventional assays or molecular testing) should be routine for healthcare providers facing an unknown fungal infection. Two critical barriers that affect the low rates for Antifungal Susceptibility Testing (AST) are low (or a lack of) sufficient insurance reimbursement rates and the low number of qualified laboratories with the capacity to perform AST. The ultimate aim is to improve the quality of patient care through fungal identification, diagnosis, and, where appropriate, susceptibility testing. Here we propose an all-encompassing call to action to address this emerging challenge.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 2","pages":"158-176"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132770","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":"Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?","authors":"Justin Harper, Michael R Betts, Mathias Lichterfeld, Michaela Müller-Trutwin, David Margolis, Katharine J Bar, Jonathan Z Li, Joseph M McCune, Sharon R Lewin, Deanna Kulpa, Dázon Dixon Diallo, Michael M Lederman, Mirko Paiardini","doi":"10.20411/pai.v8i2.665","DOIUrl":"10.20411/pai.v8i2.665","url":null,"abstract":"<p><p>Once a death sentence, HIV is now considered a manageable chronic disease due to the development of antiretroviral therapy (ART) regimens with minimal toxicity and a high barrier for genetic resistance. While highly effective in arresting AIDS progression and rendering the virus untransmissible in people living with HIV (PLWH) with undetectable viremia (U=U) [1, 2]), ART alone is incapable of eradicating the \"reservoir\" of resting, latently infected CD4⁺ T cells from which virus recrudesces upon treatment cessation. As of 2022 estimates, there are 39 million PLWH, of whom 86% are aware of their status and 76% are receiving ART [3]. As of 2017, ART-treated PLWH exhibit near normalized life expectancies without adjustment for socioeconomic differences [4]. Furthermore, there is a global deceleration in the rate of new infections [3] driven by expanded access to pre-exposure prophylaxis (PrEP), HIV testing in vulnerable populations, and by ART treatment [5]. Therefore, despite outstanding issues pertaining to cost and access in developing countries, there is strong enthusiasm that aggressive testing, treatment, and effective viral suppression may be able to halt the ongoing HIV epidemic (ie, UNAIDS' 95-95-95 targets) [6-8]; especially as evidenced by recent encouraging observations in Sydney [9]. Despite these promising efforts to limit further viral transmission, for PLWH, a \"cure\" remains elusive; whether it be to completely eradicate the viral reservoir (ie, cure) or to induce long-term viral remission in the absence of ART (ie, control; Figure 1). In a previous salon hosted by <i>Pathogens and Immunity</i> in 2016 [10], some researchers were optimistic that a cure was a feasible, scalable goal, albeit with no clear consensus on the best route. So, how are these cure strategies panning out? In this commentary, 8 years later, we will provide a brief overview on recent advances and failures towards identifying determinants of viral persistence and developing a scalable cure for HIV. Based on these observations, and as in the earlier salon, we have asked several prominent HIV cure researchers for their perspectives.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 2","pages":"115-157"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060755","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: The Chemical Characterization of the Pneumococcal Transforming Principle.","authors":"Neil S Greenspan","doi":"10.20411/pai.v8i2.687","DOIUrl":"10.20411/pai.v8i2.687","url":null,"abstract":"","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 2","pages":"177-178"},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022803","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":"HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS.","authors":"Clayton Faua, Axel Ursenbach, Anne Fuchs, Stéphanie Caspar, Frédérick Jegou, Yvon Ruch, Baptiste Hoellinger, Elodie Laugel, Aurélie Velay, David Rey, Samira Fafi-Kremer, Pierre Gantner","doi":"10.20411/pai.v8i2.638","DOIUrl":"10.20411/pai.v8i2.638","url":null,"abstract":"<p><strong>Background: </strong>Throughout HIV infection, productively infected cells generate billions of viral particles and are thus responsible for body-wide HIV dissemination, but their phenotype during AIDS is unknown. As AIDS is associated with immunological changes, analyzing the phenotype of productively infected cells can help understand HIV production during this terminal stage.</p><p><strong>Methods: </strong>Blood samples from 15 untreated viremic participants (recent infection, n=5; long-term infection, n=5; active opportunistic AIDS-defining disease, n=5) and 5 participants virologically controlled on antiretroviral therapy (ART) enrolled in the Analysis of the Persistence, Reservoir and HIV Latency (APRIL) study (NCT05752318) were analyzed. Cells expressing the capsid protein p24 (p24+ cells) after 18 hours of resting or 24 hours of stimulation (HIV-Flow) revealed productively infected cells from viremic participants or translation-competent reservoir cells from treated participants, respectively.</p><p><strong>Results: </strong>The frequency of productively infected cells tended to be higher during AIDS in comparison with recent and long-term infections (median, 340, 72, and 32/million CD4+ T cells, respectively) and correlated with the plasma viral load at all stages of infection. Altogether, these cells were more frequently CD4^low, HLA-ABC^low, CD45RA-, Ki67+, PD-1+, with a non-negligible contribution from pTfh (CXCR5+PD-1+) cells, and were not significantly enriched in HIV coreceptors CCR5 nor CXCR4 expression. The comparison markers expression between stages showed that productively infected cells during AIDS were enriched in memory and exhausted cells. In contrast, the frequencies of infected pTfh were lower during AIDS compared to non-AIDS stages. A UMAP analysis revealed that total CD4+ T cells were grouped in 7 clusters and that productive p24+ cells were skewed to given clusters throughout the course of infection. Overall, the preferential targets of HIV during the latest stages seemed to be more frequently highly differentiated (memory, T_TD-like) and exhausted cells and less frequently pTfh-like cells. In contrast, translation-competent reservoir cells were less frequent (5/million CD4+ T cells) and expressed more frequently HLA-ABC and less frequently PD-1.</p><p><strong>Conclusions: </strong>In long-term infection and AIDS, productively infected cells were differentiated and exhausted. This could indicate that cells with these given features are responsible for HIV production and dissemination in an immune dysfunction environment occurring during the last stages of infection.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 2","pages":"92-114"},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991372","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":"Time","authors":"Adrian M. Schnall","doi":"10.20411/pai.v8i2.682","DOIUrl":"https://doi.org/10.20411/pai.v8i2.682","url":null,"abstract":"Time\u0000My index finger was reaching for \u0000the up button on the elevator \u0000when the voice sounded above, \u0000Code Blue Tower 8. Code Blue Tower 8.\u0000I broke for the stairs. \u0000 \u0000They were getting the paddles in place; \u0000the First Year with the floppy hair, Ethan, \u0000pumping the chest; the Night Float,\u0000Emily, manning an Ambu-Bag;\u0000Jamie, the Resident, running the code.\u0000 \u0000I dared a look at the face – \u0000Ken, with whom I’d traded jokes \u0000for twenty years – Ken, whom I’d told \u0000yesterday his time was coming – \u0000he’d be back home, maybe two days.\u0000 \u0000Clear! barked Jamie. Hands backed away,\u0000motion suspended. A very long second.\u0000The shape on the bed gave a shudder.\u0000Then Jamie’s voice: Excellent, a rhythm.\u0000 \u0000A rhythm – but no pulse.\u0000Hands were pumping again, \u0000counting, squeezing in air. \u0000The spark was there on the screen – \u0000life, dancing across it – \u0000but none of the tiny muscles \u0000in the heart were listening. \u0000 \u0000Epi. Atropine. Thirty minutes. \u0000Ethan looked up at Jamie, she \u0000shot a glance at me. Someone \u0000had to say it – and first \u0000right of refusal to the guy \u0000with gray hair.\u0000 \u0000A power none of us wished for – \u0000a power none of us have – \u0000but the world pretends.\u0000 \u0000I felt my head move up and down.\u0000Jamie’s eyes found the clock – \u00007:44 AM, she said. Time.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"22 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139962922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Splinter","authors":"Adrian M. Schnall","doi":"10.20411/pai.v8i2.681","DOIUrl":"https://doi.org/10.20411/pai.v8i2.681","url":null,"abstract":"Splinter\u0000“Do what you need to,” I said.\u0000As though this was extractingan arrowhead buried in flesh, not a sliver of wood from a pinky.\u0000She my officemate, colleague,friend. But not – it occurred to me as she started to probe – a surgeon. Probably hadn’t fingered a forceps in years.\u0000What I warn my patients against every day – not wise to compromisewith convenience.\u0000I had no fear of pain.A dozen tours in the OR, years of drawing blood – we learn to distance, numb ourselves.\u0000Numb ourselves, that is, to the pain of another – my pinky should have taken itself to Urgent Care.\u0000Maybe there was hurt,but I never noticed. All I recall is a flood of sweetness, a drowsy warmth, as when the world is about to go dark.\u0000Sometimes as we’re fallingwe hear a voice calling in the distance.\u0000“Oh, shit – going vagal,” this one said.\u0000It sounded like mine.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139963744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}