Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. IL-17-mediated immunity driven by Th17 cells plays a crucial role in defense against this infection. However, the location and mechanism by which the Th17 immune response is induced during OPC remain unclear. Here, we show that C. albicans in the gut enhances protection against OPC. Intestinal C. albicans is taken up by the mucosal immune system and triggers a systemic C. albicans-responsive Th17 cell response. Upon oral infection with C. albicans, these Th17 cells migrate from the gut to the oral region and accumulate in the tongue tissue, resulting in antifungal immune responses. The pathobiont-reactive Th17 cells developed in the gut strongly provide IL-17A not only locally in the mouth but also systemically in the serum upon OPC. Our findings highlight that fungal pathogen-responsive Th17 cells in the gut-mouth axis enhance protection against OPC.
© 2025 The Author(s).

Hyperlipidemia induces cellular dysfunction and is strongly linked to various diseases. The transient receptor potential channel melastatin 2 (TRPM2) plays a critical role in endothelial injury, immune cell activation, and neuronal death. We reveal that TRPM2 expression in human peripheral leukocytes strongly correlates with plasma lipid levels. In middle-aged Apoe-/- mice, global, myeloid, and endothelial TRPM2 knockout or TRPM2 inhibition abolishes the hyperlipidemia-induced exacerbation of ischemic brain injury suggesting that TRPM2 overactivity caused by hyperlipidemia predisposes these cells to dysfunction during ischemia. Using a clinically relevant ischemic brain injury mouse model, we demonstrate TRPM2's pivotal role in mediating hyperlipidemia's detrimental effects on myeloid cells and neurovascular units. Our findings suggest that TRPM2 is a promising therapeutic target for alleviating neurodegenerative diseases exacerbated by hyperlipidemia, such as ischemic stroke. These results also highlight TRPM2 expression in peripheral blood as a potential biomarker for predicting stroke outcomes in hyperlipidemic patients.
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

Rubber accelerators are used in the vulcanization of rubber. However, rubber accelerators for example tetraethylthiuram disulfide (TETD) and zinc diethyldithiocarbamate (ZDEC) may cause contact allergy. Concomitant reactions between ZDEC and TETD have been observed in patients which could be explained by co- or cross-reactivity.
To investigate cross-reactivity between TETD and ZDEC and vice versa.
Groups of mice were sensitized with TETD or ZDEC based on reported EC3-values. Proliferation of lymphocytes were measured on day 5. To test cross-reactivity, mice were sensitized and challenged 3 weeks later with TETD or ZDEC. The inflammatory response was measured by changes in ear thickness and the proliferative response in CD4+ and CD8+ T cells in the submandibular and cervical draining lymph nodes.
Sensitization of mice with doses of ZDEC 3%, TETD 5.6% or TETD 16.2% induced significant increased ear thickness and proliferation of CD4+ and CD8+ T cells. Challenge with ZDEC or TETD in these groups induced significant increased ear thickness. Challenge with ZDEC in mice sensitized to TETD 5.6% or TETD 16.2% induced significant increased proliferation of CD4+ and CD8+ T cells.
We show cross-reactivity between TETD and ZDEC. Patients sensitized to TETD or ZDEC should avoid exposure to both ZDEC and TETD.
© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.

Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg after a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in the expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells, and CD8+ T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.IMPORTANCESequential boosting with mRNA vaccines has been an effective strategy to overcome waning immunity and neutralization escape by emerging SARS-CoV-2 variants. However, it remains unclear how the site of boosting relative to the primary vaccination series shapes optimal immune responses or breadth of protection against variants. In K18-hACE2 transgenic mice, we observed that intramuscular boosting with historical monovalent or variant-matched bivalent vaccines in the ipsilateral or contralateral limb elicited comparable levels of serum spike-specific antibody and antigen-specific B and T cell responses. Moreover, boosting on either side conferred equivalent protection against a SARS-CoV-2 Omicron challenge strain. Our data in mice suggest that the site of intramuscular boosting with an mRNA vaccine does not substantially impact immunity or protection against SARS-CoV-2 infection.

To investigate the impact of paracrine IL-2 signals on memory precursor (MP) cell differentiation, we activated CD8 T cell in vitro in the presence or absence of exogenous IL-2 (ex-IL-2). We assessed memory differentiation by transferring these cells into virus-infected mice. Both conditions generated CD8 T cells that participate in the ongoing response and gave rise to similar memory cells. Nevertheless, when transferred into a naive host, T cells activated with ex-IL-2 generated a higher frequency of memory cells displaying increased functional memory traits. Single-cell RNA-seq analysis indicated that without ex-IL-2, cells rapidly acquire an MP signature, while in its presence they adopted an effector signature. This was confirmed at the protein level and in a functional assay. Overall, ex-IL-2 delays the transition into MP cells, allowing the acquisition of effector functions that become imprinted in their progeny. These findings may help to optimize the generation of therapeutic T cells.
© 2024 The Authors.