Biology subjects

Audibert, A.

Publications and source records attributed to Audibert, A..

4 recordsLinked to original sources

bioRxiv2024

Toxoplasma gondii chronic infection decreases visceral nociception through peripheral opioid receptor signaling

By eliciting immune activation in the digestive tract, intestinal pathogens may perturb gut homeostasis. Some gastrointestinal infections can indeed increase the risk of developing post-infectious irritable bowel syndrome (PI-IBS). Intriguingly, the prevalent foodborne parasite Toxoplasma gondii has not been linked to the development of PI-IBS and the impact of this infection on colon homeostasis remains ill-defined. We show in a mouse model that latent T. gondii decreases visceral nociceptive responses in an opioid signaling-dependent manner. Despite the accumulation of Th1 and cytotoxic T cells in the colon of latently infected mice, the selective invalidation of enkephalin gene in T cells ruled out the involvement of T cell-derived enkephalins in hypoalgesia. These findings provide clues about how this widespread infection durably shapes the gut immune landscape and modifies intestinal physiological parameters. They suggest that in contrast to other gut microbes, T. gondii infection could be negatively associated with abdominal pain. TeaserLatent toxoplasmosis decreases gut nociception in the mouse, suggesting a negative association with abdominal pain in humans

physiology↗

bioRxiv2024

Protective function and differentiation cues of brain-resident CD8+ T cells during immune surveillance of chronic latent Toxoplasma gondii infection

Chronic T. gondii infection induces brain-resident CD8+ T cells (bTr) but their protective functions and differentiation cues remain undefined. Here, we used a mouse model of latent infection by T. gondii leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are sufficient to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection, and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner, and is associated with effective parasite control during chronic stage. Conditional invalidation of TAP-mediated MHC class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulate the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses upon T. gondii latency vs. encephalitis revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are functionally heterogeneous and autonomously ensure parasite control during T. gondii latent infection. Their differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.

immunology↗

bioRxiv2021

A neural progenitor mitotic wave is required for asynchronous axon outgrowth and morphology

Spatiotemporal mechanisms generating neural diversity are fundamental for understanding neural processes. Here, we investigated how neural diversity arises from neurons coming from identical progenitors. In the dorsal thorax of Drosophila, rows of mechanosensory organs originate from the division of sensory organ progenitor (SOPs). We show that in each row of the notum, a central SOP divides first, then neighboring SOPs divide, and so on. This centrifugal wave of mitoses depends on cell-cell inhibitory interactions mediated by SOP cytoplasmic protrusions and Scabrous, a secreted protein interacting with the Delta/Notch complex. Furthermore, when the mitotic wave was abolished, axonal growth was more synchronous, axonal terminals had a complex branching pattern and fly behavior was impaired. We show that the temporal order of progenitor divisions influences the birth order of sensory neurons, axon branching and impact on grooming behavior. These data support the idea that developmental timing controls axon wiring neural diversity.

developmental biology↗

bioRxiv2018

The BTB-ZF transcription factor Tramtrack 69 shapes neural cell lineages by coordinating cell proliferation and cell fate

Cell diversity in multicellular organisms relies on coordination between cell proliferation and the acquisition of cell identity. The equilibrium between these two processes is essential to assure the correct number of determined cells at a given time at a given place. Here, we show that Tramtrack-69 (Ttk69, a BTB-ZF transcription factor ortholog of the human PLZF factor) plays an essential role in controlling this balance. In the Drosophila bristle cell lineage, producing the external sensory organs composed by a neuron and accessory cells, we show that ttk69 loss of function leads to supplementary neural-type cells at the expense of accessory cells. Our data indicate that Ttk69 (1) promotes cell-cycle exit of newborn terminal cells by downregulating cycE, the principal cyclin involved in S-phase entry and (2) regulates cell fate acquisition and terminal differentiation by downregulating the expression of hamlet and upregulating that of Suppressor of Hairless, two transcription factors involved in neural-fate acquisition and accessory-cell differentiation, respectively. Thus, Ttk69 plays a central role in shaping neural cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate commitment.\n\nSummary statementTramtrack-69, a transcription factor orthologous to the human tumor-suppressor PLZF, plays a central role in precursor cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate determination.

developmental biology↗