Pathogens and Immunity最新文献

Background: Antibodies play a critical role in the control of pathogens and tumors through their ability to recognize non-self and then direct immune-mediated destruction. Antibodies are generated by plasma cells or plasmablasts, located throughout the tissues, and are transported between blood, lymph, mucosal secretions, and tissues to survey all sites for pathogens or malignant cells. However, mounting evidence suggests antibodies that transit across compartments (from the blood to the brain, mucosal tissues, or placenta) differ from those in systemic circulation. Whether antibodies also differ as they transit from the blood into non-privileged tissues remains unclear. Thus, here we aimed to define the landscape of antibodies that exist within the blood and tissues and begin to define the properties that lead to antibody transfer across compartments.

Methods: To analyze tissue antibodies, we performed antibody profiling in chyle, a fluid component of lymph collected via the thoracic duct, contrasting these profiles to matched plasma samples.

Results: Equivalent levels of pathogen-specific IgG antibodies and functions were observed across the plasma and lymph in people without HIV. However, this balance in IgG transfer was disrupted in people living with HIV, with significantly lower transfer ratios across several pathogen-specific IgG subpopulations in chyle.

Conclusion: Differential transfer of IgG was Fc-receptor dependent, pointing to a mechanism of transfer into tissues during inflammatory disease that may have a critical role in selecting the antibodies able to access the peripheral and lymphoid tissues.

Background: COVID-19 has caused millions of deaths and continues to burden individuals and the healthcare system. Antibodies that neutralize SARS-CoV-2 have proven to be the most reliable markers of immune protection, targets for vaccine development, and approaches for anti-viral antibody-based therapies. Measuring neutralizing antibody (NAb) titers at the bedside could inform individualized shared decision-making with patients regarding the potential benefits of repeating vaccines, use of preventative or therapeutic antibody-based therapies, and, where relevant, collection of COVID-19 convalescent plasma (CCP) with greater efficacy, especially as NAb-escape mutations have guided SARS-CoV-2 variant emergence. However, specific and accessible assays to quantify NAb levels in individuals, including the identification of potential antibody donors at the time of donation, remain unavailable. Therefore, there is a need for platforms that can be rapidly adapted to quantify serum antibody responses with known or expected correlates of protection.

Methods: In this report, we apply a novel semi-quantitative method to an established antibody lateral flow assay (sqLFA) and analyze its ability to detect the presence of functional NAbs in the serum of COVID-19-recovered individuals early in the pandemic.

Results: We found that the sqLFA has a strong positive correlation with the gold-standard microneutralization assay (specificity 80% and sensitivity 90% at a microneutralization cutoff of 1:40).

Conclusions: Taken together, the sqLFA provides a novel point-of-care-based platform for rapid readout of NAb-based immune protection to SARS-CoV-2.

The 2025 Conference on Bacteriophages: Biology, Dynamics, and Therapeutics, supported by the International Antiviral Society-USA, brought over 250 researchers, clinicians, and industry innovators from 17 countries to Washington, DC, from October 12 - 14, 2025. The meeting emphasized collaboration across the full spectrum of phage science-from molecular biology to clinical translation-reflecting a field rapidly translating novel biological insights from the laboratory into clinical applications. This summary provides highlights of the 43 oral and 97 poster presentations made during this 2.5-day conference.

Background: Human immunodeficiency virus (HIV) and Plasmodium spp., which causes malaria, are co-endemic. Previously, we showed that during antiretroviral therapy (ART)-treated simian immunodeficiency virus (SIV)/Plasmodium fragile co-infection, peripheral markers of neutrophil extracellular trap (NET) formation positively correlated with peripheral markers of disease and gastrointestinal (GI) dysfunction. However, the impact of co-infection directly in the GI mucosa is unclear. We hypothesized that ART-treated SIV/P. fragile co-infection would result in peripheral and GI immune disruption associated with exacerbated clinical manifestations of SIV and P. fragile.

Methods: Adult male rhesus macaques (RMs; n=6) were inoculated with SIVmac239, initiated ART at week 8 post-SIV infection (p.i.), were inoculated with P. fragile at week 12 p.i., and were followed until week 20 p.i. Plasma viral loads, peripheral parasitemia, and peripheral and GI immune cell frequencies and function were assessed longitudinally.

Results: We observed significant CCR5+ CD4+ T cell decline in the periphery, colon, and duodenum following SIV infection. Neutrophil frequencies were unchanged throughout ART-treated SIV/P. fragile co-infection. Notably, duodenum NET-forming granulocyte frequencies were significantly positively associated with peripheral SIV burden following P. fragile co-infection but were unassociated with peripheral parasitemia and CD4+ T cell frequencies. Finally, although P. fragile was present in the duodenum, GI parasite burden was not associated with NET-forming granulocyte frequencies, peripheral viral loads, or CD4+ T cell frequencies.

Conclusions: P. fragile co-infection during ART-treated SIV could cause mucosal disruptions that contribute to peripheral SIV replication despite ART. These data may have implications for HIV and malaria disease progression and treatment strategies.

Background: Coronary artery disease (CAD), tuberculosis (TB), and HIV are major global health concerns. Individuals affected by one or more of these conditions often exhibit chronic inflammation and immune dysregulation, with monocytes playing a central role. Monocyte subsets are known to expand in individuals with HIV, TB, or CAD, but the mechanisms by which these cells contribute to inflammation and immune responses remain poorly understood.

Methods: We employed high-dimensional mass cytometry to characterize monocyte heterogeneity in 61 Ugandan adults with varying combinations of HIV, TB, and subclinical or overt CAD. An integrative approach was used, combining manual gating, unsupervised clustering, and machine learning to identify distinct monocyte phenotypes associated with CAD and TB. Monocyte activation markers soluble CD14 (sCD14) and sCD163 were measured in plasma. CAD was diagnosed by coronary computed tomography angiography. TB was determined by a questionnaire and interferon-gamma release assay (IGRA) testing.

Results: Participants' demographics and clinical characteristics were similar by CAD or HIV/TB status. Median age was 61 years; 37.7% were female. People living with HIV and latent TB or prior active TB had higher sCD14 plasma levels compared with HIV/TB-negative individuals. Individuals with CAD showed reduced surface expression of the scavenger receptor CD163 on non-classical monocytes. Unsupervised clustering further revealed 2 distinct non-classical monocyte subsets associated with disease states: A CD86dim CX3CR1dim CD45RA+ GPR56+ CXCR3+ subset significantly depleted in individuals with CAD, and a CD86+ CX3CR1++ CD45RA++ GPR56- CD38- CXCR3- subset enriched in individuals with latent TB.

Conclusions: These findings underscore the complexity of the monocyte landscape in CAD progression, particularly in regions where HIV and TB are co-endemic. Our study reveals distinct alterations within 2 non-classical monocyte subpopulations associated with CAD and with HIV/TB, offering mechanistic insights that may support the development of precision biomarkers and immune-targeted therapies across these disease contexts.

Background: Fecal microbiota transplantation (FMT) is a standard therapy for recurrent Clostridioides difficile infection (CDI). Limited information is available on the durability of response after FMT via freeze-dried oral capsules and on whether patients who fail an initial FMT can be successfully managed with repeated FMT.

Methods: We conducted a retrospective cohort study of all patients undergoing initial FMT for recurrent CDI via freeze-dried capsules from March 2015 through June 2022 at 2 acute-care hospitals. Information on response to FMT during the initial management period (ie, 3 months after the initial FMT) and long-term durability of response was collected through direct communication with patients and medical record review. Episodes occurring within 90 days of the initial FMT were defined as recurrences, whereas those occurring more than 90 days after the initial FMT were defined as additional CDI episodes.

Results: Of 129 patients with recurrent CDI treated with FMT via freeze-dried capsules, 114 (89%) had experienced 3 or more prior episodes of CDI. At 3 months after the initial FMT, 103 (80%) patients had no recurrence, 26 (20%) patients had 1 or more recurrences managed with 1 (n=21) or 2 (n=2) additional FMTs, and 3 (12%) were transitioned to CDI suppressive therapy. During subsequent long-term follow-up (median 182 weeks), 21 of the 126 patients (17%) who did not transition to suppressive therapy had additional episodes managed with CDI therapy only (n=9), CDI therapy and additional FMT (n=10), or suppressive CDI therapy (n=2).

Conclusions: In a real-world setting with long-term follow-up, FMT via freeze-dried capsules was effective for the management of recurrent CDI. Repeated FMT procedures were effective for the management of patients with early failure after initial FMT and with additional episodes during long-term follow-up.

In this interview, Arturo Casadevall, MD, PhD, shares insight into his childhood, what motivated him to go into biomedical research, the impact of the AIDS epidemic, and the lessons learned that he imparts to younger scientists.

Background: HIV infection leads to profound alterations of gut structure, immunity, and microbiome, resulting in immune activation and inflammation, which drive the development of non-infectious comorbidities. The introduction of combination antiretroviral therapy (cART) in the chronic stages of disease does not correct such abnormalities; however, the effect of viro-suppressive treatment in the gastrointestinal tract during primary HIV infection (PHI) is largely unknown. We studied the effects of 12-week cART on gastrointestinal (GI) structure, immunity, and mucosal microbiome in people living with HIV (PLWH) with PHI.

Methods: Eleven participants with PHI enrolled in the INACTION trial underwent colonoscopy with ileum and colon biopsies, as well as peripheral blood mononuclear cell (PBMC) and plasma collection, prior to and at 12 weeks of cART. Gut biopsies were stained with CD14, CD68, CD163, and E-cadherin antibodies and Masson trichrome. Flow cytometry was performed on lamina propria and PBMCs to characterize CD4, γδ T, Treg, and Th17 cells. Gut tissue-associated microbiome analysis was conducted on colon and ileum biopsies. Ten untreated individuals with chronic HIV infection (CHI) were also studied for comparative analysis.

Results: Despite treatment of PHI, gut barrier damage (E-cadherin loss, collagen deposition) progressed, with a partially preserved distribution of intestinal macrophages. Treated PHI showed stable CD4+ and γδ T-cell frequencies and decreased activation of these subsets in the colon, with no effect on intestinal Th17 and Treg cells. No major changes in peripheral inflammation and intestinal barrier integrity markers were observed. Gut tissue-associated microbiome composition evolved during cART treatment in PHI.

Conclusion: Despite early initiation, 12-week cART is unable to correct the HIV-mediated gut damage. Since gut injury drives systemic inflammation, which in turn fosters the pathogenesis of non-communicable comorbidities, our findings provide pathogenetic evidence of limited efficacy of early cART in reverting the HIV-associated pro-inflammatory signature and clinical risk.

Dr. David Baltimore's contributions to modern biology span more than six decades and continue to shape the fields of virology, immunology, biochemistry, and molecular biology. Beyond his landmark discoveries-such as reverse transcriptase and NF-κB, as well as the Baltimore classification of viruses-his influence endures through his mentorship, leadership, and the generations of scientists he trained and inspired. In this essay, I recount my journey as his postdoctoral trainee at the California Institute of Technology, offering a personal glimpse into the mind, character, and legacy of a scientist whose approach to thinking, teaching, and living science remains timeless.