Translational Immunology Core

Multiple sclerosis (MS) is thought to be mediated by human leukocyte antigen (HLA) class II-restricted autoreactive CD4 T cells producing interleukin (IL)-17A and/or interferon γ (IFNγ), but the necessity of these cytokines for disease pathogenesis is unclear. Utilizing HLA-DR3 (DRβ1*0301) transgenic mice lacking IFNγ or IL-17A in experimental autoimmune encephalomyelitis (EAE), a model of MS, we found that neither cytokine is essential for disease induction, although both have distinct roles....

Variants in the transcription factor CRX cause a spectrum of retinal degenerative disorders including Leber congenital amaurosis 7 (LCA7). LCA7-associated variants exert a dominant effect in developing photoreceptor cells, leading to cellular dysfunction and poor to absent visual acuity in patients. Here, we dissect the allelic heterogeneity of LCA7 using multimodal single-cell gene expression and chromatin accessibility analysis of retinal organoids. We generated mature (240 day) retinal...

Measles virus (MeV) is the most contagious human respiratory pathogen. To understand how it spreads in the airways, we infected well-differentiated primary cultures of human airway epithelial cells (HAE). We discovered that the MeV attachment protein (hemagglutinin, H), the fusion (F) protein, and the assembly organizer protein (matrix, M) reach newly infected cells ahead of, and independently from, the replicative complex proteins. To characterize the mechanisms of MeV spread, we generated a...

Assembly of mature herpesvirus particles is associated with extensive rearrangement of cytoplasmic membranes. Herpes simplex virus type 1 (HSV-1) infection in neuronal cells induces the formation of a distinctive cytoplasmic viral assembly compartment (cVAC), in which rearranged host membranes and viral proteins are clustered at the perinuclear microtubule-organizing center (MTOC). Although both the trans-Golgi network (TGN) and endosomal compartments have been implicated as membrane sources for...

The human retina and underlying choroid have multiple well-organized vascular layers. However, retinal and choroidal neovascularization can develop in diseases such as diabetic retinopathy or neovascular age-related macular degeneration, which can result in destructive vision loss. Ocular macrophages are implicated in the pathogenesis of such neovascular diseases. To identify a potential pro-angiogenic macrophage subtype, we integrated 13 single-cell RNA sequencing datasets from human and mouse...

CONCLUSIONS: Observed prevalence-incidence widening gap suggests case accumulation over time and survival among continuously enrolled beneficiaries. Exacerbation burden was concentrated among individuals with prior exacerbations, chronic airway infection, and respiratory comorbidity, while exacerbation rates decreased over time across payers and subgroups, in part reflecting changes in cohort composition.

CONCLUSION: miR-451a is a pathogen-responsive, PD-associated miRNA that promotes pro-inflammatory macrophage polarization, impairs bacterialphagocytosis, and amplifies inflammation through suppression of SOCS-mediated immune regulation. These findings identify the miR-451a-SOCS3/SOCS5 axis as a potential mechanism linking bacterial challenge to dysregulated macrophage responses in PD.

SUMMARYMeasles virus (MeV) is considered the most contagious human virus. This review critically examines explanations for MeV's extraordinary transmissibility. Although substantial progress has been made in understanding MeV infection, pathogenesis, and host spread, the fundamental question of why MeV is markedly more transmissible than other structurally similar respiratory viruses within the same taxonomic families remains unresolved. Many commonly cited explanations are either incorrect,...

CONCLUSIONS: Denecimig maintained low ABRs over 52 weeks, was well tolerated, and improved patient-reported outcomes in adolescents and adults with HA with or without inhibitors.

Posttranscriptional regulation is a key mechanism by which bacteria coordinate gene expression in response to changing environments. In the human pathogen Acinetobacter baumannii, the importance of posttranscriptional gene expression control is exemplified by CsrA, a highly conserved posttranscriptional regulator that is essential for viability in multiple settings, ranging from growth in rich laboratory media to infection-relevant conditions like human serum. However, csrA is dispensable for...