Selected Grantee Publications
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- 322 results found
- Immunology
- Pediatrics
Lymph-Node-Based CD3+ CD20+ Cells Emerge From Membrane Exchange Between T Follicular Helper Cells and B Cells and Increase Their Frequency Following Simian Immunodeficiency Virus Infection
Samer et al., Journal of Virology. 2023.
https://www.doi.org/10.1128/jvi.01760-22
CD4+ T follicular helper cells are known to persist during antiretroviral therapy (ART) and have been identified as key targets for viral replication and persistence. Researchers identified a lymphocyte population that expresses CD3 (i.e., T cell lineage marker) and CD20 (i.e., B cell lineage marker) on the cellular surface in lymphoid tissues from rhesus macaques of both sexes and humans of male and female sexes. In macaques, the cells increased following simian immunodeficiency virus infection, were reduced with ART, and increased in frequency after ART interruption. These cells represent a potential area for future therapeutic strategies. Supported by ORIP (P51OD011132, U42OD011023), NIAID, NCI, NIDDK, NIDA, NHLBI, and NINDS.
Effects of Acute Femoral Head Ischemia on the Growth Plate and Metaphysis in a Piglet Model of Legg-Calvé-Perthes Disease
Armstrong et al., Osteoarthritis and Cartilage. 2023.
https://pubmed.ncbi.nlm.nih.gov/36696941/
Legg-Calvé-Perthes disease (LCPD) can lead to permanent deformity of the femoral head and premature osteoarthritis, but the underlying cause remains unknown. More work is needed to determine optimal treatment methods for LCPD. Using a piglet model for LCPD, researchers assessed the effects of acute femoral head ischemia on the proximal femoral growth plate and metaphysis. They reported that alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia. These findings suggest that growth disruption may occur sooner after the onset of ischemia than researchers had hypothesized previously. Supported by ORIP (T32OD010993, K01OD021293), NIAMS, and NCATS.
Innate Lymphoid Cells and Interferons Limit Neurologic and Articular Complications of Brucellosis
Moley et al., American Journal of Pathology. 2023.
https://www.sciencedirect.com/science/article/pii/S0002944023001980?via%3Dihub=
Brucellosis is a globally significant zoonotic disease. The current study investigated the role of innate lymphoid cells (ILCs) in the pathogenesis of focal brucellosis caused by Brucella melitensis. Following pulmonary infection with B. melitensis, mice lacking adaptive immune cells and ILCs developed arthritis, neurologic complications, and meningitis. Transcriptional analysis of Brucella-infected brains revealed marked upregulation of genes associated with inflammation and interferon responses. Collectively, these findings indicate that ILCs and interferons play an important role in prevention of focal complications during Brucella infection and that mice with deficiencies in ILCs or interferons can be used to study pathogenesis of neurobrucellosis. Supported by ORIP (T32OD011126) and NIAID.
Infection of the Maternal–Fetal Interface and Vertical Transmission Following Low-Dose Inoculation of Pregnant Rhesus Macaques (Macaca mulatta) with an African-Lineage Zika Virus
Koenig et al., PLOS ONE. 2023.
https://doi.org/10.1371/journal.pone.0284964
Researchers examined transmission of Zika virus to nonhuman primate fetuses during pregnancy. Even with a low dosage of inoculation of the dams, the investigators found that the Zika virus infected fetuses, despite the presence of a “placental fortress,” which normally protects fetuses during gestation. This transmission illustrates the high level of infectivity threat that Zika poses, which may increase if mosquitoes expand their global habitats. Understanding how Zika breaches the placental barrier will help researchers develop strategies to prevent fetal infection during pregnancy and thereby prevent adverse outcomes, such as brain malformation defects. Supported by ORIP (P51OD011106, S10OD023526), NIAID, NCI, and NIGMS.
Antibody-Dependent Cellular Cytotoxicity, Infected Cell Binding and Neutralization by Antibodies to the SIV Envelope Glycoprotein
Grunst et al., PLOS Pathogens. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10256149/
Antibodies that bind to the envelope glycoprotein (Env) on the surface of virus-infected cells can recruit cells from the immune system to kill infected cells by antibody-dependent cellular cytotoxicity (ADCC). Researchers characterized ADCC, Env binding, and neutralization in rhesus macaque antibodies that were specific for diverse epitopes of the simian immunodeficiency virus (SIV) envelope glycoprotein. They found that most antibodies that inhibit SIV infectivity also bind to Env on infected cells and mediate ADCC, but this trend was not observed in select instances. Based on these findings, the authors suggest that some antibody–Env interactions can uncouple antiviral activities. Supported by ORIP (P51OD011106) and NIAID.
Efficient Ex Vivo Expansion of Conserved Element Vaccine-Specific CD8+ T Cells from SHIV-Infected, ART-Suppressed Nonhuman Primates
Dross et al., Frontiers in Immunology. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189133/
HIV-specific T cells are necessary for control of HIV-1 replication but are largely insufficient for viral clearance. Using male rhesus macaques, investigators sought to increase the frequency of specific T cell responses in vivo using an ex vivo cell manufacturing approach. The resulting products contained high frequencies of specific, polyfunctional T cells, but no significant differences in T cell persistence were observed, nor was acquisition of simian–human immunodeficiency virus (SHIV). This work underscores this animal model as an important approach to optimize the manufacturing of antigen-specific immune effectors that can prevent virus acquisition and control viral rebound after discontinuing antiretroviral therapy (ART). Supported by ORIP (P51OD010425, U42OD011123), NIAID, and NCI.
Complement Contributes to Antibody-Mediated Protection Against Repeated SHIV Challenge
Goldberg et al., PNAS. 2023.
The first clinical efficacy trials of a broadly neutralizing antibody (bNAb) resulted in less benefit than expected and suggested that improvements are needed to prevent HIV infection. Using rhesus macaques of both sexes, investigators sought to further investigate the contribution of antibody-mediated activation of complement to the protective potency of an HIV bNAb in passive transfer and simian–human immunodeficiency virus (SHIV) challenge experiments. They observed that fewer bNAbs were required to protect animals from plasma viremia when complement activity was enhanced, suggesting that complement-mediated effector functions contribute to in vivo antiviral activity and might contribute to further improvements in the efficacy of antibody-mediated prevention strategies. Supported by ORIP (P51OD011092, U42OD023038) and NIAID.
Therapeutic Blocking of VEGF Binding to Neuropilin-2 Diminishes PD-L1 Expression to Activate Antitumor Immunity in Prostate Cancer
Wang et al., Science Translational Medicine. 2023.
Prostate cancers often escape immune detection and destruction. Investigators report that neuropilin-2 (NRP2), which functions as a vascular endothelial growth factor (VEGF) receptor on tumor cells, is an attractive target to activate antitumor immunity in prostate cancer. They found that NRP2 depletion increased T cell activation in vitro. Additionally, inhibition of the binding of VEGF to NRP2 using a mouse-specific anti-NRP2 monoclonal antibody resulted in necrosis and tumor regression. These findings provide justification for the initiation of clinical trials using this function-blocking antibody in treatment of prostate cancer, especially for patients with aggressive disease. Supported by ORIP (R24OD026440) and NCI.
Giardia Hinders Growth by Disrupting Nutrient Metabolism Independent of Inflammatory Enteropathy
Giallourou et al., Nature Communications. 2023.
https://www.nature.com/articles/s41467-023-38363-2
Giardia lamblia is one of the most common intestinal pathogens among children in low- and middle-income countries. Investigators performed translational investigations using the Malnutrition and Enteric Diseases (MAL-ED) male and female cohort, as well as mice of both sexes, to identify mechanistic pathways that might explain Giardia-induced effects on early childhood growth. They identified signatures in the urinary metabolome of young children, suggesting that host growth restriction during infection is mediated by dysregulated amino acid metabolism. Supported by ORIP (P40OD010995), NIAID, and NIDDK.
Probiotic Therapy During Vaccination Alters Antibody Response to Simian-Human Immunodeficiency Virus Infection But Not to Commensals
Wilson et al., AIDS Research and Human Retroviruses. 2023.
https://www.doi.org/10.1089/AID.2022.0123
Strategies to boost vaccine-induced mucosal humoral responses are critical to developing an HIV-1 vaccine, and probiotic supplementation could help boost antibody responses. Researchers analyzed antibody titers to explore this topic in rhesus macaques (sex not specified) infected with simian–human immunodeficiency virus (SHIV). They reported that probiotic treatment during vaccination led to delayed kinetics in the circulating HIV-specific IgA response after breakthrough SHIV infection. These findings highlight the potential of probiotic supplementation for reducing IgA-specific HIV antibodies in the plasma, which could help reduce HIV acquisition in vaccinated individuals. Supported by ORIP (P51OD011104, R21OD031435) and NIAID.