Biology subjects

Raasch, L.

Publications and source records attributed to Raasch, L..

3 recordsLinked to original sources

bioRxiv2026

Endothelial ACKR1 expression regulates neutrophil infiltration and breast cancer metastatic engraftment in the lung metastatic niche

The formation of the premetastatic niche prepares distant tissues for tumor cell engraftment. Endothelial cells are critical mediators of premetastatic niche formation, orchestrating extravasation of circulating tumor cells and critical pro-tumor immune cells, such as neutrophils. In mouse models of breast cancer, we show that primary tumors upregulate the non-signaling chemokine receptor ACKR1 in the endothelium of the lung premetastatic niche. ACKR1-expressing venules were found to be preferential sites of neutrophil and tumor cell localization within lung tissue. A newly generated conditional ACKR1 allele was used to show that endothelial-specific removal of ACKR1 expression significantly reduces metastatic engraftment in the lung. When ACKR1 is activated by tumor-secreted factors, endothelial ACKR1 functions to promote neutrophil recruitment within the lung parenchyma. We conclude that ACKR1 is a critical component of the endothelial response to tumors at the metastatic site of the lung, leading to neutrophil recruitment and promotion of tumor cell metastasis. SUMMARYEndothelial cells play critical roles in breast cancer metastasis. ACKR1 is upregulated in the endothelium of the lung metastatic niche in response to primary mammary tumors. Endothelial ACKR1 expression was found to promote neutrophil infiltration into the metastatic niche and support breast tumor cell metastasis to the lung.

cancer biology↗

bioRxiv2022

Fetal loss in pregnant rhesus macaques infected with high-dose African-lineage Zika virus

Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4-8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques inoculated with a low dose of African-lineage ZIKV at gestational day (GD) 45. Here, we inoculate eight pregnant rhesus macaques with a higher dose of African-lineage ZIKV at GD 45 to test the hypothesis that adverse pregnancy outcomes are dose-dependent. Three of eight pregnancies ended prematurely with fetal death. ZIKV was detected in both fetal and placental tissues from all cases of early fetal loss. Further refinements of this challenge system (e.g., varying the dose and timing of infection) could lead to an even more consistent, unambiguous fetal loss phenotype for assessing ZIKV countermeasures in pregnancy. These data demonstrate that high-dose inoculation with African-lineage ZIKV causes pregnancy loss in macaques and also suggest that ZIKV-induced first trimester pregnancy could be strain-specific. Author summaryAlthough pregnant rhesus macaques are susceptible to infection with Zika virus (ZIKV), fetal phenotypes can be subtle and variable. Most macaque studies of ZIKV have involved infection with Asian-lineage viruses because these viruses caused Western Hemisphere outbreaks beginning in 2015. African-lineage ZIKV yields more severe adverse fetal outcomes in small animal models. Here, we provide evidence that pregnant macaques infected late in the first trimester using a high dose of African-lineage ZIKV have frequent ZIKV-associated pregnancy loss. This severe phenotype establishes a new model for evaluating countermeasures and reinforces the idea that African-lineage ZIKV infection may be a frequent cause of pregnancy loss in areas where it is endemic depending on the amount of transmitted virus during infection.

pathology↗

bioRxiv2019

The Arabidopsis leucine-rich repeat receptor kinase MIK2 is a crucial component of pattern-triggered immunity responses to Fusarium fungi

Fusarium is a genus of fungi causing severe economic damage in many crop species exemplified by Fusarium Head Blight of wheat or Panama Disease of banana. Plants sense immunogenic patterns (termed elicitors) at the cell surface contributing to disease resistance via the activation of pattern-triggered immunity (PTI). Knowledge of such elicitors or corresponding plant immunity components is largely lacking for Fusarium species. We describe a new peptide elicitor fraction present in several Fusarium spp. which elicits canonical PTI responses in Arabidopsis thaliana but depends on a currently unknown perception mechanism. We therefore employed a forward-genetics screen using Arabidopsis plants containing a cytosolic calcium reporter (apoaequorin) to isolate fere (Fusarium Elicitor Reduced Elicitation) mutants. The fere1 mutant showed impaired PTI marker responses to an enriched elicitor fraction derived from Fusarium oxysporum but normal responses to other fungal elicitors. We mapped the causal mutation to the receptor-like kinase MIK2 (MALE DISCOVERER1-INTERACTING RECEPTOR LIKE KINASE 2) with a hitherto undescribed role in PTI pathways but documented functions in other cell surface signalling pathways. The strength of the phenotype in fere1 and independent mik2 mutants supports that MIK2 is a new key component in sensing Fusarium. Fusarium elicitor responses also partially depend on PTI signalling components known for other cell surface elicitor responses such as BAK1, BIK1, PBL1, FERONIA, LLG1 and RBOHD. This shows that Arabidopsis senses Fusarium by a novel receptor complex at the cell surface that feeds into common PTI pathways and positions MIK2 as a central player that potentially integrates plant endogenous signals with biotic and abiotic stress responses.

plant biology↗