Biology subjects

Germain, R.

Publications and source records attributed to Germain, R..

6 recordsLinked to original sources

bioRxiv2025

Immune Niche Formation in Engineered Mouse Models Reveals Mechanisms of Tumor Dormancy

Residual tumor cells can persist in a dormant state during clinical remissions that may last decades. The mechanisms that lead to such growth control vs. eventual reactivation and macroscopic tumor outgrowth remain unclear. Here, we report data from a mouse model that reveals a key role of host immunity and the cellular and molecular mechanisms that control tumor dormancy. Abrogation of myeloid-specific TGF-{beta}RII expression (T{beta}RIImyeKO) resulted in an IFN-{gamma} rich immune microenvironment. IFN-{gamma} in turn elevated KLF4-mediated SLURP1 production in malignant cells, which is critical to the tumor cell quiescent state through interruption of fibronectin-integrin signaling pathways. The dormant tumor lesions were located in spatially localized immune niches rich in NK cells, cDCs, monocytes, and neutrophils, concomitant with tumor cell inactivation of NK cell immune surveillance through a CD200-CD200R1 mechanism. Our studies identify the IFN-{gamma}-KLF4-SLURP1 and CD200-CD200R1 axes as critical molecular drivers in tumor dormancy regulated by immune-tumor crosstalk. These insights provide enhanced mechanistic understanding of tumor dormancy in a mouse model suitable for further investigation of cancer treatment resistance and prevention of metastatic spread.

cancer biology↗

bioRxiv2021

Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques

Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, particularly with respect to immune responses, we utilized the rhesus macaque model of SARS-CoV-2 infection. Two cohorts of eight older (16-23 years) and eight younger (3-5 years) rhesus macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at pre-defined timepoints in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication dynamics were limited between age cohorts. Transcriptional signatures of inflammation-associated genes in cells isolated from bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both younger and older animals. These findings suggested that age did not substantially skew major facets of acute disease in this model. However, age-specific divergence of immune responses emerged during the post-acute phase of infection (7-21 dpi). Older animals exhibited sustained local inflammatory innate responses while local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, in contrast to persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling in SARS-CoV-2-infected rhesus macaques suggests that age may delay or impair the induction of anti-viral cellular immune responses and delay efficient return to immune homeostasis following acute infection.

immunology↗

bioRxiv2020

Variance in within-pair reproductive success drives the opportunity for sexual selection annually and over the lifetimes of males in a multi-brooded songbird

In socially monogamous species, male reproductive success consists of within-pair offspring produced with their socially-paired mate(s), and extra-pair offspring produced with additional females throughout the population. Both reproductive pathways offer distinct opportunities for selection in wild populations, as each is composed of separate components of mate attraction, female fecundity, and paternity allocation. Identifying key sources of variance and covariance among these components is a crucial step towards understanding the reproductive strategies that males use to maximize fitness both annually and over their lifetimes. We use 16 years of complete reproductive data from a population of black-throated blue warblers (Setophaga caerulescens) to partition variance in male annual and lifetime reproductive success, and thereby identify if the opportunity for selection varies over the lifetimes of individual males and what reproductive strategies likely favor maximum lifetime fitness. The majority of variance in male reproduction was attributable to within-pair success, but the specific effects of individual components of variance differed between total annual and total lifetime reproductive success. Positive overall lifetime covariance between within-pair and extra-pair components indicates that males able to maximize within-pair success, particularly with double-brooding females, likely achieve higher overall lifetime fitness via both within-pair and extra-pair reproductive pathways.

evolutionary biology↗

bioRxiv2019

Biotic interactions affect fitness across latitudes, but only drive local adaptation in the tropics

Local adaptation to broad-scale environmental heterogeneity can increase species distributions and diversification, but which environmental components commonly drive local adaptation-- particularly the importance of biotic interactions--is unclear. Biotic interactions should drive local adaptation when they impose consistent divergent selection; if this is common we expect experiments to detect more frequent and stronger local adaptation when biotic interactions are left intact. We tested this hypothesis using a meta-analysis of common-garden experiments from 138 studies (149 taxa). Across studies, local adaptation was common and biotic interactions affected fitness. Nevertheless, local adaptation was neither more common nor stronger when biotic interactions were left intact, either between experimental treatments within studies (control vs. biotic interactions experimentally manipulated) or between studies that used natural vs. biotically-altered transplant environments. However, tropical studies, which comprised only 7% of our data, found strong local adaptation in intact environments but not when negative biotic interactions were ameliorated, suggesting that interactions frequently drive local adaptation in the tropics. Our results suggest that biotic interactions often fail to drive local adaptation even though they affect fitness, perhaps because the temperate-zone biotic environment is less predictable at the spatiotemporal scales required for local adaptation.

evolutionary biology↗

bioRxiv2018

The filtering metaphor revisited: competition and environment jointly structure invasibility and coexistence

Filtering, or the reduction in species diversity that occurs because not all species can persist in all locations, is thought to unfold hierarchically, at large scales due to the environment and at small scales due to competition. However, the ecological effects of competition and the environment are not independent, and observational approaches preclude investigation into their interplay. We use a demographic approach with 30 plant species to experimentally test (i) the effect of competition on species persistence in two soil moisture environments, and (ii) the effect of environmental conditions on the mechanisms underlying competitive coexistence. We find that competitors cause differential persistence of species across environments even when these effects are lacking in the absence of competition, and that the traits that determine persistence depend on the competitive environment. Changing environmental conditions generated idiosyncratic effects on coexistence outcomes, increasing competitive exclusion of some species while promoting coexistence of others. Our results highlight the importance of considering environmental filtering in light of, rather than in isolation from, competition, and challenge community assembly models and approaches to projecting future species distributions.

ecology↗

bioRxiv2018

Biodiversity on Indigenous lands equals that in protected areas

Declines in global biodiversity due to land conversion and habitat loss are driving a \"Sixth Mass Extinction\" and many countries currently fall short of meeting even nominal land protection targets to mitigate this crisis. Here, we quantify the potential contribution of Indigenous lands to biodiversity conservation using case studies of Australia, Brazil and Canada. Indigenous lands in each country are slightly more species rich than existing protected areas and, in Brazil and Canada, support more threatened species than existing protected areas or random sites. These results indicate that Indigenous lands and existing protected areas are similar in biodiversity. Enhanced partnerships between Indigenous communities and federal or state governments could help ameliorate current shortfalls in global biodiversity protection by facilitating protection for native species, helping to stem global biodiversity loss.

ecology↗