Biology subjects

Potchen, N. B.

Publications and source records attributed to Potchen, N. B..

3 recordsLinked to original sources

bioRxiv2026

Tissue-specific adaptation of human T cells is preserved during tissue inflammation

T cells play an essential role in protecting tissues against pathogens and regulating tissue homeostasis. Previous studies highlight that T cells display tissue-specific phenotypic and functional properties, suggesting that T cells adapt to their local environment. Whether inflammation disrupts tissue-specific T cell adaptation remains poorly understood. To address this open question, we examined the T cell compartment - including conventional CD4 and CD8 T cells, regulatory T cells, {gamma}{delta} T cells, and MAIT cells - from healthy and inflamed human mucosal tissues. Using high-parameter spectral flow cytometry, we examined phenotype ex vivo and the functional capacity following stimulation, utilizing conventional gating and unsupervised clustering analysis approaches. Overall, we analyzed 65 tissue samples including mild, moderate, and severely inflamed oral gingiva, healthy and inflamed lung, along with healthy and inflamed tissue from the decidual-placental interface. Across these mucosal barrier tissues, we find that tissue location plays a dominant role in shaping the composition, phenotype, and functional capacity of the T cell compartment. Importantly, these tissue-specific adaptations were largely maintained during states of tissue inflammation. This included the ability to exert tissue repair functions, which was preserved across T cell subsets, even in severely inflamed tissues.

immunology↗

bioRxiv2025

Genital herpes shedding episodes associate with alterations in the spatial organization and activation of mucosal immune cells

Herpes Simplex Virus 2 (HSV-2) infection results in variable rates of local viral shedding in anogenital skin. The impact of episodic viral exposures on immune cells in adjacent mucosal tissues, including the genital tract, is unknown. However, any immune responses at this site could impact protective mucosal immunity, tissue homeostasis, and adverse health outcomes. To investigate the impact of HSV-2 on cervicovaginal tract immunity, we applied flow cytometry, immunofluorescent imaging, analysis of soluble immune factors, and spatial transcriptomics to cervicovaginal tissue and blood samples provided by a total of 232 HSV-2 seropositive and seronegative participants, with genital HSV-2 shedding evaluated at the time of biopsy. This unique dataset was used to define and spatially map immune cell subsets and localized gene expression via spatial transcriptomics. HSV-2 seropositivity alone was associated with minimal differences in cervicovaginal and circulating T cell phenotypes. However, the vaginal mucosa during active HSV-2 shedding was associated with alterations in T cell, macrophage, and dendritic cell localization and gene expression consistent with increased immune surveillance, with immune activating and suppressing signals potentially reinforcing mucosal tissue homeostasis. SummaryIn context of episodic HSV-2 shedding, immune cells mobilize and co-localize in the vaginal epithelium, expressing cytotoxic and inflammatory genes and immunoregulatory genes that collectively may promote tissue homeostasis in settings of episodic viral shedding to limit damage.

immunology↗

bioRxiv2025

Nutrient stress dramatically increases malaria parasite clag2 copy number to increase host cell permeability and enable pathogen survival

To grow and replicate in erythrocytes, malaria parasites must increase the host cells permeability to a broad range of nutrients. The plasmodial surface anion channel (PSAC) mediates this increased permeability and has been linked to CLAG3, a protein encoded by a multigene family conserved in Plasmodium spp. Surprisingly, an CLAG3 knockout parasite produced in P. falciparum exhibits incomplete reductions in PSAC activity, propagates normally in standard nutrient-rich media, but is unable to expand in modified media with more physiological levels of key nutrients. To explore these unexpected findings, we used in vitro selections on a CLAG3-null parasite and obtained a mutant capable of expansion under nutrient-limiting conditions. This growth was associated with restored solute uptake despite absence of CLAG3 protein. The mutant parasite expressed channels with characteristics of PSAC though with altered solute selectivity and lack of protease susceptibility, suggesting a modified channel and genome-level changes in the pathogen. Whole-genome sequencing revealed a dramatically increased clag2 copy number without other relevant changes. Quantitative PCR and DNA transfection confirmed increased production of the clag2 gene product. These findings implicate CLAG2 in direct formation of nutrient channels, suggest a new model that accounts for variable expansion of clag genes in Plasmodium spp., and uncover a dramatic genome plasticity available to malaria parasites. Author SummaryMalaria parasites grow within circulating red blood cells and acquire nutrients from human and animal plasma via a pore they insert in the host membrane. This pore is linked to CLAG3, a protein conserved in all examined malaria parasites. Surprisingly, deletion of CLAG3 only partially reduces formation of the nutrient pores, allowing parasites to grow normally under standard culture conditions that provide high levels of nutrients. This CLAG3-null parasite could not grow in modified media with two nutrients reduced to levels resembling those in human plasma. Here, we used prolonged culture of the CLAG3-null parasite in nutrient-limited medium to produce a mutant that can grow at near-normal rates. Despite its inability to express CLAG3, this mutant increased its nutrient uptake using pores with altered properties. Molecular studies revealed DNA-level amplification of the gene encoding CLAG2, a closely related protein from another parasite chromosome. Our findings suggest that the human malaria parasite can change its DNA to increase nutrient uptake and grow in malnourished hosts.

microbiology↗