Biology subjects

Jenne, C. N.

Publications and source records attributed to Jenne, C. N..

4 recordsLinked to original sources

bioRxiv2026

Lung Epithelial TLR7 is a Factor in Viral Replication and Pathogenesis

Respiratory virus infections are the leading causes of morbidity and mortality of infants and the elderly worldwide. Currently it is not known how Respiratory Syncytial Virus (RSV) vaccination of infants can cause enhancement of RSV disease, highlighting gaps in our understanding about how viruses like RSV interact with the immune system. Here we address this and show that ERK MAP kinase signaling from Toll-like Receptor-7 (TLR7) detection of RSV and influenza, but not human parainfluenza virus type 3 (HPIV3), infections in bronchial epithelial cells (BECs) drives replication of the viruses. Virus infection is detected by pattern recognition receptors like TLR7 that bind to single stranded RNA (ssRNA) viral replication intermediates in late endosomes. Here we report that TLR7 is expressed in BECs and detects RSV ssRNA, causing ERK MAP kinase signaling. RSV and influenza use this detection and signaling in BECs to drive its replication and infection, a mechanism that counters TLR7s role in antiviral defence. Experimental blockade of TLR7 binding or downstream signalling through ERK MAP kinase decreased RSV and influenza replication, but had no effect on HPIV3. RSV viral loads in mouse and human females were higher compared to males, consistent with higher sex-dependent expression of the TLR7 gene from two copies of the X chromosome in females. In a TLR7 gain of function mouse model there was a significant enhancement of RSV replication and RSV eosinophilic and Th2 disease markers like interleukin-5 (IL-5). In summary, TLR7 is expressed in human lung BECs in the lungs where it acts as a factor in RSV and influenza replication and disease pathogenesis. We propose that this is a major factor in determining the sex-disparity of viral disease.

microbiology↗

bioRxiv2025

Vaccine-induced antibodies are sufficient to limit Salmonella infection in the absence of complement or macrophages.

Antibodies to Salmonella Typhimurium (STm) can protect against infection. Understanding better how antibodies, complement, and leukocytes interplay can support vaccine development. We used an Outer Membrane Vesicle (OMV) vaccine against STm to study the in vivo function of anti-STm antibodies. Using intravital microscopy, we found that upon challenge, OMV-specific antibodies promote STm uptake by spleen and liver macrophages, with neutrophils rarely capturing the bacteria. Clodronate-liposome depletion of monocytic cells reveals that these cells help prevent antigen dissemination. After vaccination and challenge of C1q, C3, C4, and C5-deficient mice, all mice except C3-deficient were protected by OMV immunization. C3-deficient mice failed to mount significant germinal center and plasma cell responses; however, after the adoptive transfer of immune sera, they had lower bacterial burdens than controls. In vitro, we showed that antibodies enhance bacterial capture in macrophages. Thus, antibodies alone are sufficient to reduce bacterial burdens, but they cooperate with complement and macrophages to maximize their functions in vivo.

immunology↗

bioRxiv2024

Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection

Inflammation-induced thrombosis is a common consequence of bacterial and viral infections, such as those caused by Salmonella Typhimurium (STm) and SARS-CoV-2. The identification of multi-organ thrombosis and the chronological differences in its induction and resolution raises significant challenges for successfully targeting multi-organ infection-associated thrombosis. Here, we identified specific pathways and effector cells driving thrombosis in the spleen and liver following STm infection. Thrombosis in the spleen is independent of IFN-{gamma} or the platelet C-type lectin-like receptor CLEC-2, while both molecules were previously identified as key drivers of thrombosis in the liver. Furthermore, we identified platelets, monocytes, and neutrophils as core constituents of thrombi in both organs. Depleting neutrophils or monocytic cells independently abrogated thrombus formation. Nevertheless, blocking TNF, which is expressed by both myeloid cell types, diminished both thrombosis and inflammation which correlates with reduced endothelial expression of E-selectin and leukocyte infiltration. Moreover, tissue factor and P-selectin glycoprotein ligand 1 inhibition impair thrombosis in both spleen and liver, identifying multiple common checkpoints to target multi-organ thrombosis. Therefore, organ-specific, and broad mechanisms driving thrombosis potentially allow tailored treatments based on the clinical need and to define the most adequate strategy to target both thrombosis and inflammation associated with systemic infections.

immunology↗

bioRxiv2019

Phospho-tuning immunity through Denisovan, modern human, and mouse TNFAIP3 gene variants

Resisting or tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here, genomic analyses of anatomically modern humans, extinct Denisovan hominins, and mice revealed a series of missense variants in the immune response inhibitor A20 (encoded by TNFAIP3), substituting non-catalytic residues of the ubiquitin protease domain to diminish I{kappa}B-dependent phosphorylation and activation of A20. Two A20 variants with partial phosphorylation deficits appeared beneficial: one originating in Denisovans and introgressed in modern humans throughout Oceania, and another in a mouse strain resistant to Coxsackievirus. By contrast, a variant with 95% loss of phosphorylation caused spontaneous inflammatory disease in humans and mice. Analysis of the partial phosphorylation variant in mice revealed diminished tolerance of bacterial lipopolysaccharide or to poxvirus inoculation as trade-offs for enhanced immunity.\n\nOne Sentence SummaryModern and ancient variants reveal a genetically tunable element for balancing immunity and microbial tolerance.

immunology↗