Biology subjects

Llano, I.

Publications and source records attributed to Llano, I..

3 recordsLinked to original sources

bioRxiv2025

Early resident NK cell response to local HIV infection in lymphoid tissue

Natural killer (NK) cells are critical mediators of antiviral immunity, yet their role in lymphoid tissues--key reservoirs of HIV persistence--remains poorly defined. Here, we uncover a distinct cytotoxic signature of tonsil-resident NK cells essential for targeting HIV-infected CD4 T cells. Using a human tonsillar model of HIV infection and extracellular matrix-based functional assays, we identify a subset of NK cells co-expressing CD69, CD49a, CD103, and the adaptive marker NKG2C as potent effectors against autologous HIV-infected tissue CD4 T cells. Both CD16 and CD16- NK subsets exhibited cytotoxic antiviral activity. However, HIV infection induced profound functional alterations in these NK cells, including dysregulated expression of CD9, TRAF2, ITGA1, suggesting disrupted activation, signaling, and tissue residency. Functional assays corroborated a significant impairment in the cytotoxic capacity, indicating HIV-driven NK cell dysfunction. Intriguingly, a subset of immature CD16-CD69 NK cells underwent functional reprogramming, transitioning into a migration-competent, and metabolically primed state, driven by the upregulation of NUMAI, LCP1, SLC38A1, MT-ND2, NUMA1, MYH9, and CD44. Functional assays confirmed this transition, revealing changes in the expression of immune checkpoint receptors and a gain of cytotoxic function in these reprogrammed cells. These findings advance our understanding of NK cell biology in HIV infection and highlight novel avenues for NK-cell-based therapeutic strategies.

immunology↗

bioRxiv2025

Identification of the Inducible HIV reservoir in Tonsillar, Intestinal and Cervical Tissue Models of HIV Latency

HIV persists in diverse tissues, with distinct cellular reservoirs presenting a major barrier to a cure and requiring targeted therapeutic strategies to address this heterogeneity. Here, we developed tissue models of HIV latency using human tonsillar, intestinal and cervicovaginal tissues. These models revealed differential HIV infection across CD4+ T cell subpopulations, with ART partially restoring CD4+ T cells and reducing intact HIV DNA. T follicular helper cells (TFH CD69+ CCR7-) were the primary inducible reservoir in tonsils, while tissue-resident memory cells (TRM CD69+ CD49a+) dominated in the intestine. Identification of markers for inducible reservoirs revealed that CD69, CD45RO, and PD-1 were shared across tissues, while CXCR5 in the tonsils and CD49a in the intestine served as tissue-specific markers. Furthermore, using different latency reversal agents (LRAs) we found that Histone Deacetylase Inhibitors (HDACis) failed to induce HIV in any tissue, the SMAC mimetic AZD5582 was effective only in a resident-memory CD4+ T cell subpopulation in the intestine, and IL15 exhibited the broadest reactivation potential across tissues and CD4+ T subsets. These models recapitulate key aspects of HIV infection providing insights into the inducible reservoirs composition in different tissues and informing strategies for its elimination.

immunology↗

bioRxiv2023

A first morphological and electrophysiological characterization of FCs of the mouse cerebellum.

The "feathered" cells of Fananas (FCs) are cerebellar glia of unknown function. Initially described more than a century ago, they have been practically absent from the scientific literature. Here, we combined whole-cell patch-clamp recordings, dye loading and near UV-laser photolysis for a first characterization of FCs in terms of their morphology, electrophysiological properties and glutamate-evoked currents. FCs were identified in cerebellar slices by their small cell bodies located in the molecular layer and stubby processes. Despite a more compact shape compared to Bergmann glia (BGs) FCs had similar membrane resistances and basal currents, suggesting electrical coupling between neighboring glia. Dye filling and pharmacological experiments confirmed homo- and heterotypic gap junction coupling among FCs and BGs. Parallel-fiber stimulation evoked in FCs a slow inward current partially blocked by NBQX, along with superimposed fast (ms) transients. Repetitive stimulations resulted in a rapid desensitization of this AMPA-receptor mediated current, which recovered for stimulation intervals >0.5s. Laser photolysis of MNI-caged glutamate replicated fast inward currents with highest current densities in the distant process. We conclude that FCs respond with fast AMPA currents to local glutamate release, and that they integrate ambient glutamate to a slow inward current. Interestingly, FCs prevail throughout adulthood with markedly different densities among cerebellar lobes. Thus, FCs are not just displaced BGs as previously suggested, but they may have lobule specific functions, both locally and at the circuit level, yet to be uncovered.

neuroscience↗