Biology subjects

Andiappan, A. K.

Publications and source records attributed to Andiappan, A. K..

4 recordsLinked to original sources

bioRxiv2025

Comparative transcriptomics of lateral hypothalamic cell types reveals conserved growth hormone-tachykinin dynamics in feeding

The lateral hypothalamus (LH) is a highly heterogeneous brain region regulating hunger and motivated behaviors. In zebrafish, the LH shows distinct neural activity across hunger, feeding, and satiety states. However, the functional and evolutionary conservation of relevant neural circuits remain unclear. Using integrative transcriptomics of zebrafish and mouse LH, we identify conserved cellular clusters with shared molecular markers, particularly within GABAergic neurons. We highlight a conserved GABAergic population expressing tachykinin and growth hormone receptors, which is responsive to food cues and modulated by hunger and feeding states. This cluster may mediate acute appetite-enhancing effects of growth hormone. In both species, feeding elevates growth hormone receptor and tachykinin expression and activates these neurons, while human growth hormone increases their activity and food intake in zebrafish. These findings suggest a conserved neural mechanism by which metabolic hormones influence feeding behavior. Our comparative LH atlas highlights the evolutionary biology of appetite regulation and the integration of hormonal and neural signals driving energy homeostasis.

neuroscience↗

bioRxiv2025

Crucial role for iron metabolism in mediating influenza A virus infection and associated disease

Rationale and ObjectivesIron availability and metabolism are important in the pathogenesis of bacterial infections. More recently, links have been reported between iron and the severity of viral infections. In this study, we characterize a crucial relationship between iron metabolism and IAV infection and disease. MethodsIron-related gene expression was assessed in human airway epithelial cells (AEC) infected with IAV. AECs were cultured with ferric iron, iron-loaded transferrin, or iron chelator, deferoxamine (DFO), prior to infection with IAV. Mice were placed on a high iron diet for 8 weeks prior to infection with IAV or treated with anti-transferrin receptor-1 (TFR1) antibody during IAV infection. The effects of iron modulation and depletion of TFR1-mediated responses on IAV infection were assessed. Measurements and main resultsIron-related gene expression and metabolism are altered systemically and in lung tissues and AECs during IAV infections. Increasing iron availability increases viral titer in AECs, while DFO protects against iron-induced increased susceptibility to infection. Increasing systemic iron loading, which increases iron levels in the lung, increases viral titer, proinflammatory responses, airway inflammation, and worsens IAV-induced disease in terms of lung function and weight loss in vivo. Inhibition of TFR1 protects against IAV-induced disease in vivo. ConclusionIAV infections remain a major threat to human health and global economies. Strategies that boost protective, or reduce pathogenic, host responses may provide broadly effective, long-term therapeutic options. We have identified a key role for iron metabolism in modifying host responses to IAV that can be harnessed to protect against disease. Key MessagesO_LIIron metabolism is altered systemically, and in airway epithelial cells and lung tissues, during IAV infection. C_LIO_LIIncreased iron availability increases viral titer both in vitro and in vivo C_LIO_LISystemic iron loading worsens IAV-induced inflammation and disease outcomes in vivo, highlighting iron as a crucial factor for modulating IAV infections and disease. C_LIO_LIHost epithelial cells and lung tissues reduce TFRC gene expression, whilst the number and proportion of TFR1hi expressing cells increase, in response to IAV infection. Neutralising TFR1 protects against IAV-induced disease in vivo, highlighting TFR1 as a potential therapeutic target for IAV infections. C_LI

immunology↗

bioRxiv2025

Single-cell omics-based characterization of human basophils reveals two transcriptionally distinct populations

BackgroundBasophils are implicated in various diseases including allergies, but a comprehensive characterization of human basophils has yet to be performed at the single-cell level. ObjectiveWe aimed to generate a single-cell omics-based resource of circulating human basophils, to be made accessible to the research community. We also sought to investigate basophil heterogeneity at the transcriptional and surface epitope levels. MethodsCirculating basophils were analyzed using short- and long-read single-cell RNA-sequencing in combination with large-scale immunoprofiling of more than 100 cell surface markers. ResultsWe used a cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) based cell barcoding system to accurately track side scatterlow lineage- CCR3+ Fc{varepsilon}RI+ basophils through the single-cell omics analysis. The approach allowed for accurate transcriptional profiling of basophils among low-density peripheral blood leukocytes. The generation of an additional dataset with only basophils revealed two transcriptionally distinct populations. Single-cell transcriptomic analysis of samples from additional donors was performed and coupled with a large-scale immunoprofiling screen, producing a third CITE-seq dataset containing basophils. The analysis verified the existence of the two transcriptionally distinct populations and revealed that these populations have similar immunophenotypes with regard to the investigated surface markers. Long-read single-cell RNA-sequencing analysis provided further insights into the gene expression dynamics of the circulating basophils and confirmed the transcriptionally defined basophil states. ConclusionsThe single-cell omics analysis revealed two transcriptionally distinct basophil populations. Our single-cell omics resource constitutes a reference for charting human basophils at the cellular and molecular levels in health and disease. Capsule summaryShort- and long-read single-cell RNA-sequencing coupled with large-scale immunoprofiling characterize human basophils in peripheral blood and reveal two transcriptionally distinct populations.

immunology↗

bioRxiv2022

Soluble signal inhibitory receptor on leukocytes-1 is released from activated neutrophils by proteinase 3 cleavage

Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human granulocytes and monocytes which dampens antimicrobial functions. We previously showed that sputum neutrophils from infants with severe respiratory syncytial virus (RSV) bronchiolitis have decreased SIRL-1 surface expression compared to blood neutrophils, and that SIRL-1 surface expression is rapidly lost from in vitro activated neutrophils. This led us to hypothesize that activated neutrophils lose SIRL-1 by ectodomain shedding. Here, we developed an ELISA and measured the concentration of soluble SIRL-1 (sSIRL-1) in RSV bronchiolitis and hospitalized COVID-19 patients, which are both characterized by neutrophilic inflammation. In line with our hypothesis, sSIRL-1 concentration was increased in sputum compared to plasma of RSV bronchiolitis patients, and in serum of hospitalized COVID-19 patients compared to control serum. In addition, we show that in vitro activated neutrophils release sSIRL-1 by proteolytic cleavage, which can be prevented by proteinase 3 inhibition. Finally, we found that SIRL-1 shedding is prevented by extracellular adherence protein (Eap) from S. aureus. Notably, we recently showed that SIRL-1 is activated by PSM3 from S. aureus, suggesting that S. aureus may counteract SIRL-1 shedding to benefit from preserved inhibitory function of SIRL-1. In conclusion, we are the first to report that SIRL-1 is released from activated neutrophils by proteinase 3 cleavage and that endogenous sSIRL-1 protein is present in vivo.

immunology↗