Single-cell analysis reveals ESX-1-mediated accumulation of permissive macrophages in infected mouse lungs.

(MTB) ESX-1, a type VII secretion system, is a key virulence determinant contributing to MTB's survival within lung mononuclear phagocytes (MNPs), but its effect on MNP recruitment and differentiation remains unknown. Here, using multiple single-cell RNA sequencing techniques, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow-derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden.

Type 1 lymphocytes and interferon-γ accumulate in the thalamus and restrict seizure susceptibility after traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide and can lead to secondary sequelae such as increased seizure susceptibility. Emerging work suggests that the thalamus, the relay center of the brain that undergoes secondary damage after cortical TBI, is involved with heightened seizure risks after TBI. TBI also induces the recruitment of peripheral immune cells, including T cells, to the site(s) of injury, but it is unclear how these cells impact neurological sequelae post-TBI.

CZ CELLxGENE Discover: a single-cell data platform for scalable exploration, analysis and modeling of aggregated data.

Hundreds of millions of single cells have been analyzed using high-throughput transcriptomic methods. The cumulative knowledge within these datasets provides an exciting opportunity for unlocking insights into health and disease at the level of single cells. Meta-analyses that span diverse datasets building on recent advances in large language models and other machine-learning approaches pose exciting new directions to model and extract insight from single-cell data.

Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior.

The innate immune system shapes brain development and is implicated in neurodevelopmental diseases. It is critical to define the relevant immune cells and signals and their impact on brain circuits. In this work, we found that group 2 innate lymphoid cells (ILC2s) and their cytokine interleukin-13 (IL-13) signaled directly to inhibitory interneurons to increase inhibitory synapse density in the developing mouse brain.

BiP/GRP78 is a pro-viral factor for diverse dsDNA viruses that promotes the survival and proliferation of cells upon KSHV infection.

The Endoplasmic Reticulum (ER)-resident HSP70 chaperone BiP (HSPA5) plays a crucial role in maintaining and restoring protein folding homeostasis in the ER. BiP's function is often dysregulated in cancer and virus-infected cells, conferring pro-oncogenic and pro-viral advantages. We explored BiP's functions during infection by the Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic gamma-herpesvirus associated with cancers of immunocompromised patients.