Biology subjects

Deka, A.

Publications and source records attributed to Deka, A..

5 recordsLinked to original sources

bioRxiv2024

Modeling the transmission dynamics of African swine fever virus within commercial swine barns: Quantifying the contribution of multiple transmission pathways

Transmission of the African swine fever virus (ASFV) within commercial swine barns occurs through direct and indirect pathways. Identifying and quantifying the roles of ASFV dissemination within barns is crucial for the development of effective disease control strategies. We developed a stochastic transmission model to examine the ASFV dissemination dynamics through eight transmission routes within commercial swine barns. We consider seven transmission routes at three disease dynamics levels: within-pens, between-pens, and within-room transmission, along with the transfer of pigs between pens within the same room. We simulated ASFV spread within barns of various sizes and layouts from rooms with a median of 32 pens (IQR:28-40), where each pen housing a median of 34 pigs (IQR: 29-36). Our model enables the tracking of the viral load in each pen and the monitoring of the disease status at the pen level. Simulation results show that between-pen transmission pathways exhibited the highest contribution to ASFV spread, accounting for 71.4%, where within-pen and within-room pathways account for 20.1% and 8.5%, respectively. Among the direct transmission pathways, nose-to-nose contact between pens was the primary route of dissemination, comprising an average of 49%, while the fecal transmission between pens contributed 21%. On the other hand, aerosol transmission within pens had the lowest contribution, accounting for less than 1%. Furthermore, we show that the daily transfer of pigs between pens did not impact the spread of ASFV. The combination of passive surveillance of daily detection and active surveillance focused on mortality allowed the detection of ASFV within three Days, with peak detection occurring when mortality rates peaked. The model also allows us to pinpoint where the majority of infections and viral load are concentrated during the ASFV spread. This work significantly deepens our understanding of ASFV spread within commercial swine production farms in the U.S. and highlights the main transmission pathways that should be prioritized when implementing ASFV countermeasure actions at the room level.

ecology↗

bioRxiv2024

Modeling the impact of optimized airflow and sick pen management on the spread of infectious diseases in swine barns

The airborne spread of infectious livestock diseases plays a crucial role in the propagation of epidemics, particularly in populations confined to densely populated facilities, such as commercial swine barns. Therefore, quantitative assessments for the performance of barn ventilation systems may serve as an alternative biocontainment control strategy to reduce the spread of infectious pathogens. In this study, we present a framework to simulate airborne disease dissemination within swine barns and facilitate the strategic design of control actions, including optimization of ventilation and placement of sick animals (sick pen). This framework is based on a susceptible-infected-recovered (SIR) model that accounts for the between-pen disease spread within swine barns. A pen-to-pen contact network is used to construct a transmission matrix according to the transport of airborne respiratory pathogens across pens in the barns, via our Reynolds-averaged Navier-Stokes computational fluid dynamics (CFD) solver. By employing this CFD-augmented SIR model, we demonstrated that the location of the sick pen and the barn ventilation configuration played crucial roles in modifying disease dissemination dynamics at the barn level. In addition, we examined the effect of natural ventilation through different curtain adjustments. We observed that curtain adjustments either suppress the disease spread by an average of 56.5% or exacerbate the outbreak potential by an average of 5.7%, compared to the scenario where side curtains are not raised. Furthermore, we optimize the ventilation configuration via the selection and placement of ventilation fans through the integration of the CFD-augmented framework with the genetic algorithm to minimize the dissemination of swine disease within barns. Compared to regular barn ventilation settings, our optimized ventilation system significantly reduced disease spread by an average of 43.2%. Our study emphasizes the role of airborne transmission and a strategy for sick pen management in controlling the spread of within-barn disease.

bioengineering↗

bioRxiv2023

Non-canonical NF-κB signaling in dendritic cells promotes intestinal inflammation by restraining the tolerogenic β-catenin-Raldh2 axis

Dendritic cell (DC) dysfunctions exacerbate intestinal pathologies. However, the mechanisms compromising DC-mediated immune controls remain unclear. We found that intestinal DCs from mice subjected to experimental colitis possessed heightened non-canonical NF-{kappa}B signaling, which activates the RelB:p52 heterodimer. Genetic inactivation of this pathway in DCs alleviated inflammation in colitogenic mice. Unexpectedly, RelB:p52 deficiency diminished the transcription of Axin1, a critical component of the {beta}-catenin destruction complex. This reinforced {beta}-catenin-driven expression of Raldh2, which imparts tolerogenic DC attributes by promoting retinoic acid (RA) synthesis. Indeed, DC-specific non-canonical NF-{kappa}B impairment improved the colonic frequency of Tregs and IgA+ B cells, which fostered luminal IgA and eubiosis. Introducing {beta}-catenin haploinsufficiency in non-canonical NF-{kappa}B-deficient DCs moderated Raldh2 activity, reinstating colitogenic sensitivity in mice. Finally, IBD patients displayed a deleterious non-canonical NF-{kappa}B signature in intestinal DCs. In sum, we establish a DC network that integrates non-canonical NF-{kappa}B signaling to subvert RA metabolic pathway in fueling intestinal inflammation. Significance (100)Distorted dendritic cell (DC) functions have been implicated in aberrant intestinal inflammation; however, the underlying mechanism remains obscure. We discovered that the non-canonical NF-{kappa}B pathway exacerbates inflammation in the colitogenic gut by downmodulating {beta}-catenin-driven synthesis of Raldh2 in DCs. Raldh2 represents a key enzyme involved in the production of tolerogenic retinoic acid in intestinal DCs. Beyond regulating immune genes, therefore, non-canonical NF-{kappa}B signaling appears to instruct retinoic acid-mediated control of gut health. While we illustrate a DC network integrating immune signaling and micronutrient metabolic pathways in the intestine, our finding may have broad relevance for nutritional interventions in inflammatory ailments. eToCDeka and Kumar et al. illustrate a DC-circuitry that exacerbates intestinal inflammation in IBD patients and colitogenic mice. Non-canonical NF-{kappa}B signaling restrains {beta}-catenin in DCs to downmodulate Raldh2, which promotes tolerogenic RA synthesis, leading to diminished Treg and IgA+ cell frequencies in the gut. HighlightsO_LIAberrant intestinal inflammation is associated with and exacerbated by non-canonical NF-{kappa}B signaling in DCs. C_LIO_LINon-canonical signaling restrains the tolerogenic {beta}-catenin-Raldh2 axis in DCs by upregulating Axin1. C_LIO_LIDC-specific RelB:p52 impairment promotes {beta}-catenin-dependent Treg accumulation in the gut. C_LIO_LIA DC defect of non-canonical signaling causes {beta}-catenin-dependent increase in luminal sIgA, fostering the gut microbiome. C_LI One sentenceThe non-canonical NF-{kappa}B pathway fuels intestinal inflammation by waning the tolerogenic {beta}-catenin-Raldh2-retinoic acid axis in DCs.

immunology↗

bioRxiv2023

A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis

Hepatic factors secreted by the liver promote homeostasis and are pivotal for maintaining the liver-gut axis. Bile acid metabolism is one such example wherein, bile acid synthesis occurs in the liver and its biotransformation happens in the intestine. Dysfunctional interactions between the liver and the intestine stimulate varied pathological outcomes through its bidirectional portal communication. Indeed, aberrant bile acid metabolism has been reported in inflammatory bowel disease (IBD). However, the molecular mechanisms underlying these crosstalks that perpetuate intestinal permeability and inflammation remain obscure. Here, we identify a novel hepatic gene program regulated by Rela and Stat3 that accentuates the inflammation in an acute experimental colitis model. Hepatocyte-specific ablation of Rela and Stat3 reduces the levels of primary bile acids in both the liver and the gut and shows a restricted colitogenic phenotype. On supplementation of chenodeoxycholic acid (CDCA), knock-out mice exhibit enhanced colitis-induced alterations. This study provides persuasive evidence for the development of multi-organ strategies for treating IBD and identifies a hepatocyte-specific rela-stat3 network as a promising therapeutic target.

immunology↗

bioRxiv2020

An epithelial Nfkb2 pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module

Aberrant inflammation associated with human ailments, including inflammatory bowel disease (IBD), is typically fuelled by the inordinate activity of RelA/NF-{kappa}B transcription factors. As such, the canonical NF-{kappa}B module mediates controlled nuclear activation of RelA dimers from the latent cytoplasmic complexes. What provokes pathological RelA activity in the colitogenic gut remains unclear. The noncanonical NF-{kappa}B pathway promotes immune organogenesis involving Nfkb2 gene products. Because NF-{kappa}B pathways are intertwined, we asked if noncanonical signaling aggravated inflammatory RelA activity. Our investigation revealed frequent engagement of the noncanonical pathway in human IBD. In a mouse model, an Nfkb2 function exacerbated gut inflammation by amplifying the epithelial RelA activity induced upon intestinal injury. Our mechanistic studies clarified that cell-autonomous Nfkb2 signaling supplemented latent NF-{kappa}B dimers leading to hyperactive canonical RelA response in the inflamed colon. In sum, regulation of latent NF-{kappa}B dimers links noncanonical signaling to RelA-driven inflammatory pathologies and may provide for therapeutic targets. In briefNoncanonical NF-{kappa}B signals in intestinal epithelial cells supplement latent RelA dimers that, in turn, aggravated canonical NF-{kappa}B response in the colitogenic gut exacerbating intestinal inflammation. HighlightsO_LIHuman IBD involves the frequent engagement of the noncanonical NF-{kappa}B pathway. C_LIO_LIMice deficient in the noncanonical signal transducer Nfkb2 are resistant to experimental colitis. C_LIO_LINoncanonical NF-{kappa}B signaling supplements latent RelA NF-{kappa}B dimers. C_LIO_LINoncanonical NF-{kappa}B signaling amplifies canonical NF-{kappa}B response to TLR ligands. C_LI

immunology↗