Fraser, I. | Search bioRxiv

bioRxiv2024

IL-10 dependent adaptation allows macrophages to adjust inflammatory responses to TLR4 stimulation history

Macrophages must scale inflammation to the trajectories of infections, escalating as pathogen loads rise, resolving as they fall. The cytokine IL-10 and its chromatin-level effector BCL-3 are critically important anti-inflammatory agents, yet how they avoid muting newly recruited cells before those cells read their own pathogen input has been unclear. Applying systematically varied consecutive TLR4 (Kdo2-Lipid A) stimuli to bone marrow-derived macrophages, we identify two coupled features. First, macrophages retain a quantitative memory of prior stimulation: only when a secondary TLR stimulus matches or exceeds a prior one, I{kappa}B degradation, NF-{kappa}B/MAPK activation, and cytokine output increase. Second, IL-10 susceptibility is itself gated by TLR4 history: even a 100-fold IL-10 excess fails to suppress TNF- in weakly primed cells. Both trace to history- and IL-10-dependent BCL-3 recruitment with p65 displacement at the Tnf {kappa}B site. Modeling shows how this licensing logic enables trajectory-aware responses that clear pathogens while limiting tissue damage.

immunology↗

bioRxiv2022

Variation in near-surface soil temperature drives plant assemblage insurance potential

O_LIStudying how assemblages vary across environmental gradients provides a baseline for how assemblages may respond to climate change. Per the biological insurance hypothesis, assemblages with more variation in functional diversity will maintain ecosystem functions when species are lost. In complement, environmental heterogeneity supports landscape-scale ecosystem functionality (i.e. spatial insurance), when that variation includes environments with more abundant resources. C_LIO_LIWe use the relationship between vascular plant functional diversity and microenvironment to identify where assemblages are most likely to maintain functionality in a mountainous fieldsite in northeastern Utah, USA. We assessed how life history strategies and information about phylogenetic differences affect these diversity-environment relationships. C_LIO_LIWe found less functionally dispersed assemblages, that were shorter and more resource-conservative on hotter, more variable, south-facing slopes. In contrast, we found more functionally dispersed assemblages, that were taller and more resource-acquisitive on cooler, less variable, north-facing slopes. Herbaceous and woody perennials drove these trends. Additionally, including information about phylogenetic differences in a dispersion metric indicated that phylogeny accounts for traits we did not measure. C_LIO_LISynthesis. At our fieldsite, soil temperature acts as an environmental filter across aspect. If soil temperature increases and becomes more variable, the function of north- vs. south-facing assemblages may be at risk for contrasting reasons. On south-facing slopes, assemblages may not have the variance in functional diversity needed to respond to more intense, stressful conditions. Conversely, assemblages on north-facing slopes may not have the resource-conservative strategies needed to persist if temperatures become hotter and more variable. We suggest that studying dispersal traits, especially of perennial species, will provide additional insight into whether this landscape will maintain function as climate changes. C_LI

ecology↗