Human Immunology Core

Chlamydia trachomatis (C.t.) is the causative agent of several human diseases, including the sexually transmitted infection chlamydia and the eye infection trachoma. As an obligate intracellular bacterial pathogen, invasion is critical for establishing infection and subsequent pathogenesis. During invasion, C.t. secretes effector proteins via its type III secretion system (T3SS), which manipulate host actin cytoskeletal regulation to promote bacterial entry. Previous studies identified the T3SS...

Optic neuritis (ON), or inflammation of the optic nerve, is a common presenting symptom of demyelinating neuroinflammatory conditions that result in significant, subacute vision loss. Given its association with visual impairment and varying extent of visual recovery, ON has been recognized as a significant health burden with a need for new therapeutic strategies to improve long-term visual outcomes. Among the resources utilized to study ON, animal models have emerged as powerful tools to examine...

Polychlorinated biphenyls (PCBs) are a group of environmental toxicants associated with increased risk of diabetes, obesity, and metabolic syndrome. These metabolic disorders are characterized by systemic and local inflammation within adipose tissue, the primary site of PCB accumulation. These inflammatory changes arise when resident adipose tissue macrophages undergo phenotypic plasticity-switching from an antiinflammatory to an inflammatory phenotype. Thus, we sought to assess whether PCB...

CONCLUSIONS: This data suggests that the addition of CPH:SA IL-1αMPs to RT may boost anti-tumor immune response and target both local and systemic disease. This combination is worthy of further investigation as an immunotherapeutic strategy and could represent a promising approach to improve survival outcomes in HNSCC patients.

CONCLUSION: The Telenephrology Dashboard was developed using a Human-Centered Design approach to improve remote nephrology consultations. Future efforts will focus on evaluating its impact on user satisfaction, referring clinician satisfaction, access to nephrology care, and patient care outcomes.

Plasmodium parasites undergo development and replication within hepatocytes before infecting erythrocytes and initiating clinical malaria. Although type I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers a pathway of lysosomal fusion with the parasitophorous vacuole...

Immune thrombotic thrombocytopenic purpura (iTTP) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular occlusion secondary to acquired ADAMTS13 deficiency. Contemporary data regarding iTTP treatment practices in the US, including the use of caplacizumab, are lacking. We aimed to characterize the demographics and therapies, including medications and apheresis practices, in patients with iTTP in the US. We retrospectively analyzed iTTP cases at 15 sites in the...

Production of antibodies against protein-based therapeutics (e.g., monoclonal antibodies (mAbs)) by a recipient's immune system can vary from benign symptoms to chronic neutralization of the compound, and in rare cases, a lethal cytokine storm. One critical factor that can induce or contribute to an anti-drug antibody (ADA) response is believed to be the presence of aggregated proteins in protein-based therapeutics. There is a high level of variability in the aggregation of different proteins,...

Early detection of viral infection and rapid activation of host antiviral defenses through transcriptional upregulation of interferons (IFNs) and IFN-stimulated genes (ISGs) are critical for controlling infection. However, aberrant production of IFN in the absence of viral infection leads to auto-inflammation and can be detrimental to the host. Here, we show that the DNA-binding transcriptional repressor complex composed of Capicua (CIC) and Ataxin-1 like (ATXN1L) binds to an 8-nucleotide motif...

Type 2 inflammatory diseases are common in cystic fibrosis (CF) including asthma, sinusitis, and allergic bronchopulmonary aspergillosis. CD4+ T helper 2 (Th2) cells promote these diseases through secretion of IL-4, IL-5, and IL-13. Whether the cystic fibrosis transmembrane conductance regulator (CFTR), the mutated protein in CF, has a direct effect on Th2 development is unknown. Using murine models of CFTR deficiency and human CD4+ T cells, we show CD4+ T cells expressed Cftr transcript and...