Search bioRxiv⌕ Search

Biology subjects

Wells, E.

Publications and source records attributed to Wells, E..

4 recordsLinked to original sources

Lung adventitial fibroblasts support type 2 Tregs to shape the response to influenza infection

Viral pneumonias are lung infections that lead to both short- and long-term complications, including acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Lung stromal-immune interactions balance pathogen clearance with excessive immune-mediated injury, and healthy lung repair with necessary scarring. Here, we define the lung spatiotemporal stromal-immune response to Influenza A virus (IAV) infection, focusing on the underappreciated role of fibroblasts and their dynamic states. We used 3D quantitative microscopy and scRNAseq to identify IAV-driven fibroblast states, including inflammatory fibroblasts, profibrotic fibroblasts, and adventitial fibroblasts (AFs). Unexpectedly, loss of fibroblast TGF{beta} signaling led to early enhancement of immuno-modulatory AFs, driving activation of tissue-resident type 2 regulatory T cells (T2-Tregs) and ultimately improving lung functional outcomes. In vitro co-culture systems additionally revealed that AFs act as a niche to support T2-Tregs. Our data suggest an intimate fibroblast-immune crosstalk is required to temporally and spatially balance lung tissue inflammation and repair.

immunology↗

The emerging fungal pathogen Candida auris induces IFNγ to colonize mammalian hair follicles

Public health alarm concerning the emerging fungus Candida auris is fueled by its antifungal drug resistance and propensity to cause deadly outbreaks. Persistent skin colonization drives transmission and lethal sepsis although its basis remains mysterious. We compared the skin colonization dynamics of C. auris with its relative C. albicans, quantifying skin fungal persistence and distribution and immune composition and positioning. C. auris displayed a higher propensity to colonize hair follicles and avidly bound to human hair. While C. albicans triggered an effective sterilizing type 3/17 antifungal immune response driven by IL-17A/F-producing lymphocytes, C. auris triggered a type 1, IFN{gamma}-driven immune response targeting hair follicles. Rather than promoting fungal clearance, IFN{gamma} enhanced C. auris skin colonization by acting directly on keratinocytes impairing epithelial barrier integrity and repressing antifungal defense programs. C. auris exploits focal skin immune responses to create a niche for persistence in hair follicles.

immunology↗

Cellular mechanisms underlying beneficial versus detrimental effects of bacterial antitumor immunotherapy

Bacteria engineered to express tumor antigens as a cancer vaccine have yielded mixed results. Here, we utilized an attenuated strain of Listeria monocytogenes ({Delta}actA, Lm) that does not express tumor antigen to explore the immunological response to Listeria itself in the context of intravenous (IV), intratumoral (IT), or a combination of IV+IT administration into tumor-bearing mice. Unexpectedly, we found that Lm persisted in tumors of immune competent mice, regardless of the administration route. While IT Lm alone led to the recruitment of immunosuppressive immune cells that promoted tumor growth, IV Lm followed by IT Lm controlled tumor growth. IV Lm vaccination generated a pool of anti-Lm cytotoxic CD8 T cells that killed Lm-infected non-tumor cells to control tumor growth both indirectly, by limiting cancer cell proliferation, and directly, by enhancing tumor-specific T cell responses. Our findings reveal a differential impact of IT Lm administration on tumor progression that depends on the presence of anti-Lm CD8 T cells, which alone are sufficient to promote therapeutic efficacy.

immunology↗

Low plastic ingestion rate in Atlantic Cod (Gadus morhua) from Newfoundland destined for human consumption collected through citizen science methods

Marine microplastics are a contaminant of concern because their small size allows ingestion by a wide range of marine life. Using citizen science during the Newfoundland recreational cod fishery, we sampled 205 Atlantic cod (Gadus morhua) destined for human consumption and found that 5 had eaten plastic, an ingestion prevalence rate of 2.4%. This ingestion rate for Atlantic cod is the second lowest recorded rate in the reviewed published literature (the lowest is 1.4%), and the lowest for any fish in the North Atlantic. This is the first report for plastic ingestion in fish in Newfoundland, Canada, a province dependent on fish for sustenance and livelihoods.\n\nHighlights (3-5 points, 85 char max including spaces)O_LIPlastic ingestion rate of 2.4% for Atlantic Cod (n=205)\nC_LIO_LIFirst recorded baseline for fish in Newfoundland, Canada\nC_LIO_LIThis plastic ingestion prevalence rate is among the lowest recorded to date\nC_LIO_LIUsed citizen science to collect GI tracts from fish destined for human consumption\nC_LI

ecology↗