Project description:To understand the mechanistic basis of local innate and adaptive immunity against infectious bronchitis virus (IBV) at the molecular level, we examined the gene transcription profile of tracheal epithelial layers at 3 days after infection of chickens with an attenuated IBV-Massachusetts strain. Keywords: Disease State Analysis, Early mucosal immune response, FHCRC 13k chicken array
Project description:Immunological mechanisms of susceptibility to NTM disease are poorly understood. We evaluated innate and antigen-specific adaptive immune responses to Mycobacterium avium complex in individuals with MAC lung disease. We investigated the gene expression changes induced in PBMCs by polyclonal stimulation (anti-CD3, anti-CD28), Mav and Mtb lysates and a peptide pool (MTB300) in individuals with MAC lung disease (MACDZ), and healthy controls (IGRA+ and IGRA-).
Project description:Lymph nodes (LNs) enable innate defense to limit pathogen dissemination while also driving adaptive immunity. Yet, certain innate responses can restrict adaptive processes, suggesting that these must be tightly regulated. Here, we report that after infection or immunization, LN architecture is rapidly altered, with large-scale, polarized recruitment of neutrophils and monocytes from inflamed blood vessels, and intranodal repositioning of NK cells. Mechanistically, dendritic cells (DCs) promote this process through expression of inflammatory chemokines and integrin ligands. While necessary for efficient pathogen containment, DC-driven innate cell responses paradoxically limit early adaptive immunity, with infiltrating neutrophils displacing lymphocytes and reducing the LN area available for T cell priming. Upon threat secession however, DCs and DC-recruited monocytes phagocytose the neutrophils, restoring tissue architecture and generating polarized domains for downstream adaptive immune cell activation. Thus, DCs orchestrate innate cell organization during inflammation, serving as rheostats of innate versus adaptive functions of the LN.
Project description:The cancer-immunity cycle is regulated by a series of stimulatory and inhibitory factors. The Stimulator of Interferon Genes (STING) pathway, a key stimulator of type I interferon production, bridges innate and adaptive immunity to promote anti-tumor responses. Using a syngeneic pancreatic tumor model, we characterized the single-cell landscape changes induced by STING stimulation. Our findings revealed that STING agonist treatment reprograms transcription across multiple cell lineages, boosting innate immune responses and lymphocyte activation, thereby enhancing tumor killing. Single-cell transcriptome sequencing identified significant increases in monocytes, neutrophils, macrophages, and CD8 T cells, indicating augmented tumor inflammation. Differential gene expression analysis highlighted upregulated genes related to immune cell effector mechanisms and antigen presentation. Functional assays confirmed that STING activation enhances T cell-mediated tumor killing through myeloid cell activation. These results underscore the potential of STING agonists in reprogramming the tumor microenvironment to potentiate anti-tumor immunity, although clinical translation remains challenging due to pharmacokinetic limitations and potential systemic toxicity. Further research is needed to optimize STING agonist delivery and dosage for effective cancer immunotherapy.