Biology subjects

Mannion, J. M.

Publications and source records attributed to Mannion, J. M..

3 recordsLinked to original sources

bioRxiv2026

IL-17 producing tissue-resident memory T-cells expanded during Staphylococcus aureus nasal colonisation provide heterologous immune protection.

Staphylococcus aureus persistently colonises the nasal tissue (NT) of a significant proportion of the population. The long-lasting impact that asymptomatic S. aureus exposure has on immune memory at colonised barrier sites is incompletely understood, potentially impacting vaccine responsiveness in a pre-exposed population. Tissue resident memory (TRM) cells are long-lived T-cells which remain poised at barrier sites for localised reactivation following antigen exposure. This study demonstrates an increase in NT CD4+ and {gamma}{delta}+ TRM cells in response to S. aureus colonisation, which undergo expansion and IL-17 production upon secondary S. aureus exposure. Interestingly, these cells were also capable of non-specific reactivation, with IL-17+ TRM cells in S. aureus colonised mice enhancing protection against K. pneumoniae infection. Ex-vivo data suggest that non-specific CD4+ TRM cell re-activation is pro-inflammatory cytokine dependent, but antigen independent. Overall, these findings demonstrate that S. aureus nasal colonisation shapes long-lasting TRM cell responses in the NT, which have the potential for non-specific bystander reactivation during subsequent heterologous infection.

immunology↗

bioRxiv2026

Type 2 conventional dendritic cells and regulatory T cells form a barrier tissue circuit to control allergic inflammation

Chronic allergic diseases are driven by T helper type 2 (Th2) cells in barrier tissues. Despite their profound effects on tissue physiology, Th2 cells represent a rare cell population within tissues, suggesting mechanisms restraining Th2 cell expansion at barrier sites that remain ill defined. Using a murine model of allergic asthma, we demonstrate that effector Th2 cells promote cDC2 activation within the lungs, including expression of the CCR4 ligands that attract Foxp3+ regulatory T cells (Tregs). Selective deletion of Ccr4 in Tregs during the effector Th2 cell response led to increased lung Th2 cells, activated cDC2s, and allergic inflammation. Mechanistically, CCR4 promoted Treg trafficking efficiency and was required to specifically control tissue cDC2 co-stimulatory molecule expression. Lastly, in the airways of humans with allergy, the expression of the CCR4 ligands in activated cDCs correlated with Treg enrichment. In sum, we define a cDC2-Treg feedback circuit within a barrier tissue that restrains effector Th2 cell expansion, revealing a novel role for tissue cDC2s in controlling Th2 cell biology.

immunology↗

bioRxiv2023

Respiratory tract Moraxella catarrhalis and Klebsiella pneumoniae can promote pathogenicity of myelin-reactive Th17 cells

The respiratory tract is home to a diverse microbial community whose influence on local and systemic immune responses is only beginning to be appreciated. The airways have been linked with trafficking of myelin-specific T cells in the pre-clinical stages of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Th17 cells are important pathogenic effectors in MS and EAE but are innocuous immediately following differentiation. Upregulation of the cytokine GM-CSF appears to be a critical step in their acquisition of pathogenic potential, but little is known about the mechanisms that mediate this process. Here, primed myelin-specific Th17 cells were transferred to congenic recipient mice prior to exposure to various human respiratory tract-associated bacteria and T cell trafficking, phenotype and the severity of resulting EAE monitored. Disease was exacerbated in mice exposed to the Proteobacteria Moraxella catarrhalis and Klebsiella pneumoniae, but not the Firmicute Veillonella parvula, and this was associated with a significant increase in GM-CSF+ and GM-CSF+IFN{gamma}+ ex-Th17-like donor CD4 T cells in the lungs and CNS of these mice. These findings support the concept that respiratory bacteria may contribute to the pathophysiology of CNS autoimmunity by modulating pathogenicity in crucial T cell subsets that orchestrate neuroinflammation.

immunology↗