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Cuenca, A.

Publications and source records attributed to Cuenca, A..

3 recordsLinked to original sources

Whole genome sequencing reveals a novel Renibacterium salmoninarum lineage and suggests geographic endemism combined with anthropogenic spread in the North-East Atlantic area

Renibacterium salmoninarum is the causative agent of bacterial kidney disease (BKD) and has been isolated from northern European salmonid farms since the 1960s. The bacterium has been detected only sporadically in Norway during the last decades, but the country experienced several geographically spread outbreaks since December 2022. The phylogenomic relationships of R. salmoninarum isolates associated with the epizootics ongoing on the West Coast and in Mid-Norway were explored using a whole genome sequencing approach. A broad overview of the phylogeography of this pathogen was gained through sequencing and analysis of a collection of isolates from Norway (n=67), Iceland (n=12), Denmark (n=12), and the Faroe Islands (n=1), along with a collection of 109 publicly available sequences. We identified two distinct contemporary clades of R. salmoninarum causing BKD in Norway in the period 2022-2024. Both clades belong to the expanding, aquaculture-associated Lineage 1. The epidemiological picture appears consistent with contemporary aquaculture operations, raising questions on the effectiveness or practice of current biosecurity practices towards R. salmoninarum. Our work also describes a hitherto undescribed lineage (Lineage 3), predominantly from Iceland, where BKD is considered endemic. The detection of endemic reservoirs of R. salmoninarum in European water systems underscores the potential for ongoing pathogen circulation independent of acute outbreaks. This finding emphasizes the importance of further investigation of the mechanisms of pathogen persistence, particularly within environments related to aquaculture, where chronic infection reservoirs could compromise disease management and biosecurity. IMPORTANCERenibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD), is a chronic salmonid pathogen that often presents subclinically, complicating detection and control. Effective management of BKD is therefore crucial for sustainable aquaculture and wild fish conservation. Recognizing the need for comprehensive sampling, previous studies have underscored the importance of a global isolate collection to better understand the epidemiology of the pathogen. While the slow genetic evolution and highly conserved genome of the bacterium have reduced the resolution of conventional typing methods in the past, applying whole genome sequencing has enabled its molecular tracing at the outbreak level. Here, we present the largest phylogenomic analysis of R. salmoninarum to date, including sequences from Denmark, Iceland, and the Faroe Islands for the first time. This expanded dataset elucidates past and present movements of the pathogen in European waters, providing actionable insights to support development of targeted BKD management and biosecurity strategies.

genomics↗

Adjuvant conditioning enhances neutrophil function while inducing a suppressive peritoneal macrophage phenotype

Adjuvants are widely used to boost the immune response during vaccination protocols. Our group has previously reported that repeated intraperitoneal administration of alum in mice, known as adjuvant conditioning (AC), creates an immunosuppressive environment that delays allogeneic graft rejection through NLRP3-dependent MDSC expansion. However, little is known about the effects of AC on the reprogramming of peritoneal cavity cells, particularly the different peritoneal macrophage populations and the effects in the adaptive immune response. We found a population-specific immune response to alum, with small peritoneal macrophages (SPMs) being more prone to inflammasome activation than large peritoneal macrophages (LPMs) in vitro. In vivo, alum exposure led to NLRP3-dependent macrophage disappearance reaction (MDR) of LPMs, which could be explained by aggregate formation and migration to the omentum. AC also induced the reprogramming of resident macrophages and infiltrating monocytes towards a less inflammatory state, making them more vulnerable to bacterial infections, but recruited neutrophils with enhanced killing ability. This suggests that AC may influence both innate and adaptive immunity in distinct ways, reprogramming cells to different profiles, indicating its potential as an immunosuppressive treatment for autoimmune diseases and transplant rejection.

immunology↗

Host-derived oxidized phospholipids initiate effector-triggered immunity fostering lethality upon microbial encounter.

Macrophages detect invading microorganisms via pattern recognition receptors that recognize pathogen-associated molecular patterns, or via sensing the activity of virulence factors that initiates effector-triggered immunity (ETI). Tissue damage that follows pathogen encounter leads to the release of host-derived factors that participate to inflammation. How these self-derived molecules are sensed by macrophages and their impact on immunity remain poorly understood. Here we demonstrate that, in mice and humans, host-derived oxidized phospholipids (oxPLs) are formed upon microbial encounter. oxPL blockade restricts inflammation and prevents the death of the host, without affecting pathogen burden. Mechanistically, oxPLs bind and inhibit AKT, a master regulator of immunity and metabolism. AKT inhibition potentiates the methionine cycle, and epigenetically dampens Il10, a pluripotent anti-inflammatory cytokine. Overall, we found that host-derived inflammatory cues act as "self" virulence factors that initiate ETI and that their activity can be targeted to protect the host against excessive inflammation upon microbial encounter.

immunology↗