Biology subjects

Le Gros, G.

Publications and source records attributed to Le Gros, G..

5 recordsLinked to original sources

bioRxiv2024

Basophils drive the resolution and promote wound healing in adult and aged mice

An active resolution is critical to control the duration of inflammation and limit its pathological consequences. Defects in resolution during wound healing allow the emergence of chronic wounds, a common complication in the elderly. Here, we show that basophils infiltrate the periphery of mouse skin wounds for at least three weeks, during both the inflammation and resolution phases of wound healing. Depletion of basophils induces an increased secretion of inflammatory molecules, accumulation and activation of pro-inflammatory leukocytes, and delays the wound healing response. Basophils particularly promote epidermal differentiation towards homeostasis in the wounds. Basophil-derived IL-4 and M-CSF drive partly their immunoregulatory and healing properties. Unexpectedly, aged mice basophils infiltrate more potently the wounds to promote inflammation resolution, showing a transcriptomic signature biased towards tissue remodeling. Thus, basophils are not pro-inflammatory but pro-resolution cells during an essential biological process such as skin wound healing. Unraveling basophil pro-resolution properties may reveal new strategies to fight chronic wounds in the elderly. SUMMARYThe resolution of inflammation is essential for homeostasis and becomes defective with age. Here we show basophil immunoregulatory properties promote resolution during skin wound healing, in both adult and aged mice.

immunology↗

bioRxiv2023

Helminth infection driven gastrointestinal hypermotility is independent of eosinophils and mediated by alterations in smooth muscle instead of enteric neurons

Intestinal helminth infection triggers a type 2 immune response that promotes a weep-and sweep response characterised by increased mucus secretion and intestinal hypermotility, which function to dislodge the worm from its intestinal habitat. Recent studies have discovered that several other pathogens cause intestinal dysmotility through major alterations to the immune and enteric nervous systems (ENS), and their interactions, within the gastrointestinal tract. However, the involvement of these systems has not been investigated for helminth infections. Eosinophils represent a key cell type recruited by the type 2 immune response and alter intestinal motility under steady-state conditions. Our study aimed to investigate whether intestinal dysmotility driven by murine hookworm, Nippostrongylus brasiliensis, infection involves eosinophils and how the ENS and smooth muscles of the gut are impacted. Eosinophil deficiency did not influence helminth-induced intestinal hypermotility and hypermotility did not involve gross structural or functional changes to the ENS. Hypermotility was instead associated with a dramatic increase in smooth muscle thickness and contractility. In summary our data indicate that, in contrast to other pathogens, helminth-induced intestinal hypermotility is driven by largely by myogenic, rather than neurogenic, alterations with such changes occurring independently of eosinophils. (<300 words) Author SummaryIntestinal helminth infection is a global threat to those living in poverty without adequate sanitation. Expulsion of intestinal worms is driven by a host type 2 immune response, characterised by increased eosinophils, that results in the intestinal hypermotility and mucus secretion that dislodge the worm from its luminal habitat. Intestinal motility is largely controlled by the local enteric nervous system (ENS) and can be regulated by close interactions between neurons and intestinal immune cells. Utilising Nippostrongylus brasiliensis as a model of murine hookworm infection, we investigated the contribution of the ENS and eosinophils to intestinal hypermotility and worm expulsion. Despite the critical role of the ENS in regulating typical intestinal function, very little alteration to ENS structure or function was observed following N. brasiliensis infection. Instead, infected animals displayed dramatically increased smooth muscle thickness and contractile strength. Neither helminth-induced intestinal hypermotility nor altered smooth muscle morphology required eosinophils. Our findings reveal that, in contrast to other intestinal pathogens, myogenic rather than neurogenic alterations drive small intestinal hypermotility and pathogen expulsion following hookworm infection. (<200 words)

immunology↗

bioRxiv2021

The skin environment controls local dendritic cell differentiation and function through innate IL-13

The signals driving the adaptation of type-2 dendritic cells (DC2s) to diverse peripheral environments are not well understood. We show that the development of CD11blow migratory DC2s, a DC2 population unique to the dermis, requires STAT6- and KLF4-dependent IL-13 signaling, whereas DC2s in lung and small intestine are STAT6-independent. Dermal IL-13 is mostly derived from innate lymphoid cells expressing a resting ICOS+ KLRG1-ST2-phenotype. Analysis of public datasets indicates that human skin DC2s also express an IL-4/IL-13 gene signature compared to blood or spleen, suggesting a similar developmental pathway in mice and humans. In the absence of IL-13 signaling, dermal DC2s are stable in number but remain CD11bhi and show defective activation in response to allergen with diminished ability to support IL-4+ GATA3+ Th development, whereas anti-fungal IL-17+ ROR{gamma}t+ responses are increased. Thus, steady-state IL-13 fosters a non-inflammatory and pro-allergic environment in healthy skin via conditioning of local DC2s.

immunology↗

bioRxiv2019

Single-cell analysis of intestinal immune cells during helminth infection

Single cell isolation from helminth infected intestines has been notoriously difficult, due to the strong anti-parasite type 2 immune responses that drive mucus production, tissue remodeling and immune cell infiltration. Through the systematic optimization of a standard intestinal digestion protocol, we were able to isolate millions of immune cells from heavily infected tissues. Using this protocol, we validated many hallmarks of anti-parasite immunity and analyzed immune cells from the lamina propria and granulomas during helminth development, as well as acute and chronic worm infection.

immunology↗

bioRxiv2017

De novo long-read assembly of a complex animal genome

Eukaryotic genome assembly remains a challenge in part because of the prevalence of complex DNA repeats. This is a particularly acute problem for holocentric nematodes because of the large number of satellite DNA sequences found throughout their genomes. These have been recalcitrant to most genome sequencing methods. At the same time, many nematodes are parasites and some represent a serious threat to human health. There is a pressing need for better molecular characterization of animal and plant parasitic nematodes. The advent of long-read DNA sequencing methods offers the promise of resolving complex genomes. Using Nippostrongylus brasiliensis as a test case, applying improved base-calling algorithms and assembly methods, we demonstrate the feasibility of de novo genome assembly matching current community standards using only MinION long reads. In doing so, we uncovered an unexpected diversity of very long and complex DNA repeat sequences, including massive tandem repeats of tRNA genes. The method has the added advantage of preserving haplotypic variants and so has the potential to be used in population analyses.

genomics↗