Biology subjects

Mulka, K.

Publications and source records attributed to Mulka, K..

4 recordsLinked to original sources

bioRxiv2026

Metabolomics of in vivo inflammation identifies soluble sialic acid as a conserved myeloid-cell metabolite

During an immune response, metabolism changes dramatically. Metabolites are oxidized to power immune cell functions, serve as building blocks for proliferation, and act as effectors to regulate pathogen or host cells. Though metabolic changes in cultured cells have been studied extensively, metabolism changes in vivo are less understood. Here, we measured metabolomic changes across six mouse tissues in three models of immune activation: CpG-DNA cytokine storm, lymphocytic choriomeningitis virus infection, and polyI:C viral mimetic injection; and carried out metabolomics in cultured macrophages activated with different stimuli. We found most metabolomic changes were exclusive to either inflamed tissues or cultured macrophages, although itaconate was strongly induced in both contexts. We then mechanistically dissected the role of the soluble sialic acid N-glycolylneuraminic acid, which is highly induced in inflamed tissues yet only modestly in cultured macrophages. This metabolite rises in tissues in different models of inflammation, and the analogous human metabolite, N-acetylneuraminic acid, is increased in human patients experiencing inflammation. We found that N-glycolylneuraminic acid is produced in CD11b+ myeloid cells by cleavage of protein-bound sialic acid. However, blocking its production did not affect CpG-DNA liver inflammation or LCMV infection in mice. Therefore, these experiments identify soluble sialic acid as a conserved biomarker of inflammation in mice and humans and highlight the differences in metabolism between in vitro and in vivo models of inflammation.

biochemistry↗

bioRxiv2023

Pathogenesis of Breakthrough Infections with SARS-CoV-2 Variants in Syrian Hamsters

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has evolved into multiple variants. Animal models are important to understand variant pathogenesis, particularly for those with mutations that have significant phenotypic or epidemiological effects. Here, cohorts of naive or previously infected Syrian hamsters (Mesocricetus auratus) were infected with variants to investigate viral pathogenesis and disease protection. Naive hamsters infected with SARS-CoV-2 variants had consistent clinical outcomes, tissue viral titers, and pathology, while hamsters that recovered from initial infection and were reinfected demonstrated less severe clinical disease and lung pathology than their naive counterparts. Males had more frequent clinical signs than females in most variant groups, but few sex variations in tissue viral titers and lung pathology were observed. These findings support the use of Syrian hamsters as a SARS-CoV-2 model and highlight the importance of considering sex differences when using this species. ImportanceWith the continued circulation and emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, understanding differences between the initial and a subsequent reinfection on disease pathogenesis is critical and highly relevant. This study characterizes Syrian hamsters as an animal model to study reinfection with SARS-CoV-2. Previous infection reduced the disease severity of reinfection with different SARS-CoV-2 variants.

microbiology↗

bioRxiv2021

Progression and Resolution of SARS-1 CoV-2 Infection in Golden Syrian Hamsters

To catalyze SARS-CoV-2 research including development of novel interventive and preventive strategies, we characterized progression of disease in depth in a robust COVID-19 animal model. In this model, male and female golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 USA-WA1/2020. Groups of inoculated and mock-inoculated uninfected control animals were euthanized at day 2, 4, 7, 14, and 28 days post-inoculation to track multiple clinical, pathology, virology, and immunology outcomes. SARS-CoV-2-inoculated animals consistently lost body weight during the first week of infection, had higher lung weights at terminal timepoints, and developed lung consolidation per histopathology and quantitative image analysis measurements. High levels of infectious virus and viral RNA were reliably present in the respiratory tract at days 2 and 4 post-inoculation, corresponding with widespread necrosis and inflammation. At day 7, when infectious virus was rare, interstitial and alveolar macrophage infiltrates and marked reparative epithelial responses (type II hyperplasia) dominated in the lung. These lesions resolved over time, with only residual epithelial repair evident by day 28 post-inoculation. The use of quantitative approaches to measure cellular and morphologic alterations in the lung provides valuable outcome measures for developing therapeutic and preventive interventions for COVID-19 using the hamster COVID-19 model.

pathology↗

bioRxiv2018

miRNA profiling of primate cervicovaginal lavage and extracellular vesicles reveals miR-186-5p as a potential retroviral restriction factor in macrophages

The goal of this study was to characterize extracellular vesicles (EVs) and miRNAs of primate cervicovaginal lavage (CVL) during the menstrual cycle and simian immunodeficiency virus (SIV) infection, and to determine if differentially regulated CVL miRNAs might influence retrovirus replication. CVL and peripheral blood were collected from SIV-infected and uninfected macaques. EVs were enriched by stepped ultracentrifugation and characterized thoroughly. miRNA profiles were assessed with a medium-throughput stem-loop/hydrolysis probe qPCR platform and validated by single qPCR assays. Hormone cycling was abnormal in infected subjects, but EV concentration correlated with progesterone concentration in uninfected subjects. miRNAs were present predominantly in the EV-depleted CVL supernatant. Only a small number of CVL miRNAs were found to vary during the menstrual cycle or SIV infection. Among them was miR-186-5p, which was depleted in retroviral infection. In experiments with infected macrophages in vitro, this miRNA inhibited HIV replication. These results provide further evidence for the potential of EVs and small RNAs as biomarkers or effectors of disease processes in the reproductive tract.

molecular biology↗