Pathogens and Immunity最新文献

Background: Susceptibility to common infectious diseases is often linked to innate immune deficiencies. Patients may present normal standard immunological profiles but remain highly vulnerable to infections, complicating diagnosis. This study investigates innate and intrinsic immune deficiencies and their genetic underpinnings in Moroccan patients, emphasizing early detection and personalized care.

Methods: A retrospective analysis was conducted using data from the Moroccan Inborn Errors of Immunity (IEI) registry (2008-2024). Included were patients with confirmed innate or intrinsic immunodeficiencies based on CBC, CRP, immunoglobulin levels, lymphocyte subpopulations, and whole-exome sequencing. Classification followed the 2022 IUIS criteria.

Results: Among 884 patients with IEI, 79 (∼9%) had innate or intrinsic immunodeficiencies, with genetic confirmation in 46 (58%). Of these, 23 (50%) were diagnosed with Mendelian susceptibility to mycobacterial disease (MSMD), involving mutations in the IL12RB1, STAT1, IFNGR1, SPPL2A, TYK2, and TBX21 (T-bet) genes. Chronic mucocutaneous candidiasis (CMC) was found in 15 (32%) patients, linked to STAT1 and IL17RA mutations. Severe viral infection predisposition was seen in 3 patients (POLR3A, IFIH1, TLR7XL) and bacterial susceptibility in 3 others (IRF4, IFNGR1, NCSTN). Novel variants were identified, including IRAK4 c.277delT (p.F93fsX26), not previously reported, and SNORA31 (n.36T>C), previously seen in Saudi Arabia, now found in a Moroccan case of herpes simplex encephalitis.

Conclusion: This study reveals the genetic complexity of innate immune disorders in Morocco, with a notable prevalence of MSMD and CMC. It underscores the value of early genetic screening to guide diagnosis and improve patient outcomes.

Background: Endophthalmitis, a severe infection of the intraocular tissues that can result in permanent loss of vision if not immediately treated, is often caused by fungi, namely Candida albicans. Treatment options are limited due to a lack of ocular penetration of antifungal drugs. Rezafungin, an echinocandin antifungal with a long half-life, which was recently approved by the US Food and Drug Administration (FDA), has shown efficacy against candidiasis.

Methods: In this study, using a rabbit model, we compared rezafungin, micafungin, and voriconazole in a hematogenous C. albicans endophthalmitis rabbit model. Fungal burden was determined in the aqueous humor, vitreous humor, choroid-retina, and the kidneys of infected rabbits; eye lesions were visualized by indirect ophthalmoscopy.

Results: No fungal growth was detected in the aqueous humor, vitreous humor, or choroid-retina of rabbits treated with 10 mg/kg rezafungin at the time of fungal inoculation. Additionally, rabbits given 10 mg/kg rezafungin showed the lowest kidney fungal burden (average log colony-forming units [CFUs]/g of < 0.5). In contrast, animals given either micafungin (6.2 mg/kg) or voriconazole (10 mg/kg) in the same treatment regimen were positive for fungal infection as measured by CFUs in each of these areas, demonstrating fungal burden. Additionally, significant increases in eye lesion scores were observed in rabbits given either micafungin or voriconazole, while no eye lesions were noted in rabbits that received rezafungin.

Conclusion: Taken together, these results indicate that rezafungin was effective at reducing the acute fungal burden and subsequent eye lesions caused by C. albicans-induced endophthalmitis.

Antiretroviral therapy (ART) can effectively control human immunodeficiency virus (HIV) replication; however, lifelong treatment is required due to viral reservoirs, which fuel viral rebound. This necessitates curative interventions that can achieve either eradication of the reservoir or durable remission off ART. Advances in technology have fostered development of multi-omic techniques encompassing molecular tools, proteomic analyses, imaging, and artificial intelligence (AI)-driven data analysis to understand HIV reservoir biology and persistence. These have informed the investigation of therapeutic interventions such as broadly neutralizing antibodies, latency reversal, immune cell augmentation, antivirals, and gene therapy. From April 7-10, 2025, experts in the field convened at the Keystone Symposia conference, HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, to discuss novel strategies for eradication and/or durable ART-free control of HIV.

Stanley Plotkin, M.D., reflects on his professional journey, describing how formative educational experiences influenced his career. He discusses his contributions to vaccine development, notably for rubella and rotavirus, and shares insight on advancements in vaccine technology, including strengths and limitations of mRNA and DNA platforms. Dr. Plotkin emphasizes the importance of adapting public health recommendations as scientific understanding evolves, discusses the challenges of establishing mucosal immunity, and highlights the benefits of combining vaccines. He also offers thoughtful perspectives on natural versus vaccine-induced immunity, drawing upon his extensive expertise. Finally, he touches on his personal interest in learning to fly.

In this engaging interview, Dr. John Perfect reflects on his distinguished career in infectious diseases, focusing on his early scientific interests, his pivotal experiences during the emergence of HIV/AIDS, and his extensive research on fungal pathogens, particularly Cryptococcus. Dr. Perfect discusses the evolution of antifungal therapies, the challenges of drug resistance, the promise of molecular diagnostics and immunotherapies, and the complexities faced in clinical research. He emphasizes the importance of mentorship and optimism for future generations of scientists, concluding with a message of hope and encouragement for ongoing innovation and resilience in medical science.

Background: Circulating degranulated platelets have been described during acute SARS-CoV-2 infection and associated with COVID-19 complications. This study investigated the relationship between the presence of plasma SARS-CoV-2 RNA (ie, SARS-CoV-2 RNAemia), systemic inflammation, and platelet dysfunction in a group of patients with COVID-19. Unlike our previous publication, which focused on platelet characterization, this work explores potential determinants of platelet activation, based on a distinct subset of patients with available stored samples.

Methods: Patients with COVID-19 were stratified by platelet δ-granule content using the luciferin/luciferase assay into 2 groups: normal (COV_δ-norm) and low (COV_δ-low). Plasma SARS-CoV-2 RNAemia (RT-qPCR), cytokines, and chemokines (Cytometric Bead Array) were quantified on plasma samples. Markers of platelet activation were measured by flow cytometry in whole blood.

Results: A total of 75 patients with COVID-19 were enrolled; 57 presented normal levels of platelet δ-granule content (COV_δ-norm) and 18 had low levels of platelet δ-granules (COV_δ-low). Groups were comparable in terms of age, sex, comorbidities, and SARS-CoV-2 RNAemia levels. Patients in the COV_δ-low group showed significantly higher chemokine and cytokine levels compared to those in the COV_δ-norm group, with strong correlations between IL-6, as well as granulocyte-macrophage colony-stimulating factor (GM-CSF), with platelet degranulation parameters. A similar trend, albeit less pronounced, was observed when patients were stratified based on their platelet activation phenotype.

Conclusions: These findings suggest that peripheral inflammation, rather than SARS-CoV-2 RNAemia, is associated with platelet dysfunction during acute SARS-CoV-2 infection.

Background: Despite the control of Bordetella pertussis with vaccine introduction, the incidence of pertussis has increased in the United States and globally. New vaccine strategies are clearly needed to regain control of this vaccine-preventable infection.

Methods: Experimental pertussis infection of baboons induces an acute respiratory illness with clinical and laboratory features similar to whooping cough in man. In a previous study, acellular pertussis-vaccinated (aP) baboons were protected from clinical illness but not from prolonged airway colonization. In contrast, convalescent baboons are protected from both clinical illness and colonization. These studies suggest that current aP vaccines may be ineffective at preventing airway colonization, contributing to resurgence of pertussis.

Results: In studies conducted at the University of Massachusetts Chan Medical School in Worcester, Massachusetts, mucosal IgG antibody responses in nasopharyngeal washes are similar in convalescent and vaccinated baboons. However, significantly higher mucosal anti-pertussis immunoglobulin A (IgA) responses are observed in convalescent animals.

Conclusions: These studies suggest that mucosal IgA responses to some pertussis antigens will result in bacterial clearance.