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Avila-Cariño, Javier
Alternative names
Publications (3 of 3) Show all publications
Stratoulias, V., Ruiz, R., Kanatani, S., Osman, A. M., Keane, L., Armengol, J. A., . . . Joseph, B. (2023). ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain. Nature Neuroscience, 26, 1008-1020
Open this publication in new window or tab >>ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
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2023 (English)In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 26, p. 1008-1020Article in journal (Refereed) Published
Abstract [en]

Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1– microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
urn:nbn:se:umu:diva-209132 (URN)10.1038/s41593-023-01326-3 (DOI)000986066100001 ()37169859 (PubMedID)2-s2.0-85159060710 (Scopus ID)
Åke Wiberg FoundationSwedish Cancer SocietyWenner-Gren FoundationsAcademy of Finland, 309489Academy of Finland, 324177The Swedish Brain FoundationSwedish Research CouncilSwedish Childhood Cancer Foundation
Available from: 2023-06-07 Created: 2023-06-07 Last updated: 2023-06-07Bibliographically approved
Lopez Chiloeches, M., Bergonzini, A., Martin, O. C. B., Bergstein, N., Erttmann, S. F., Aung, K. M., . . . Frisan, T. (2023). Genotoxin-producing Salmonella enterica induces tissue-specific types of DNA damage and DNA damage response outcomes. Frontiers in Immunology, 14, Article ID 1270449.
Open this publication in new window or tab >>Genotoxin-producing Salmonella enterica induces tissue-specific types of DNA damage and DNA damage response outcomes
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2023 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1270449Article in journal (Refereed) Published
Abstract [en]

Introduction: Typhoid toxin-expressing Salmonella enterica causes DNA damage in the intestinal mucosa in vivo, activating the DNA damage response (DDR) in the absence of inflammation. To understand whether the tissue microenvironment constrains the infection outcome, we compared the immune response and DDR patterns in the colon and liver of mice infected with a genotoxigenic strain or its isogenic control strain.

Methods: In situ spatial transcriptomic and immunofluorescence have been used to assess DNA damage makers, activation of the DDR, innate immunity markers in a multiparametric analysis.

Result: The presence of the typhoid toxin protected from colonic bacteria-induced inflammation, despite nuclear localization of p53, enhanced co-expression of type-I interferons (IfnbI) and the inflammasome sensor Aim2, both classic features of DNA-break-induced DDR activation. These effects were not observed in the livers of either infected group. Instead, in this tissue, the inflammatory response and DDR were associated with high oxidative stress-induced DNA damage.

Conclusions: Our work highlights the relevance of the tissue microenvironment in enabling the typhoid toxin to suppress the host inflammatory response in vivo.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
bacterial genotoxin, DNA damage response, inflammasome, inflammation, tissue specificity
National Category
Immunology Microbiology
urn:nbn:se:umu:diva-220315 (URN)10.3389/fimmu.2023.1270449 (DOI)001150445700001 ()38274797 (PubMedID)2-s2.0-85183041210 (Scopus ID)
Swedish Cancer Society, 20 0699 PjFSwedish Research Council, 2021-00960The Kempe Foundations, SMK-1962The Kempe Foundations, JCK-1826The Kempe Foundations, JCK-3110Cancerforskningsfonden i Norrland, AMP20-993Cancerforskningsfonden i Norrland, AMP 17-884
Available from: 2024-02-13 Created: 2024-02-13 Last updated: 2024-02-13Bibliographically approved
Bergonzini, A., Avila-Cariño, J., Lopez Chiloeches, M. & Frisan, T. The challenge of establishing immunocompetent human intestinal 3D models.
Open this publication in new window or tab >>The challenge of establishing immunocompetent human intestinal 3D models
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Expression of typhoid toxin in Salmonella Typhimurium causes DNA damage, activating the DNA damage response (DDR), in absence of an inflammatory response in the colonic mucosa of infected mice. The anti-inflammatory effect is tissue specific and is not observed in the liver, suggesting that the local immune microenvironment modulates the DDR outcome.

To assess the role of the immune cells in the DDR outcome induced by the genotoxigenic Salmonella, we have initiated the development of an immunocompetent 3D colonic mucosal model based on a collagen matrix containing colonic fibroblasts and different subtypes of immune cells, overlayed with colonic epithelial cells.

Embedding of peripheral blood mononuclear cells in the collagen matrix did not influenced either the tissue integrity or the activation of the DDR, observed exclusively upon infection with the genotoxigenic strain. However, embedding of T cells, monocytes, or non-polarized macrophages altered the pattern of the DDR and the toxin specific effect was lost. Presence of macrophages was further associated with alteration of the epithelial layer integrity. This effect was infection-dependent, but not toxin specific.

Our data demonstrated that addition of immune cells to a 3D mucosal model altered the DDR induced by a genotoxigenic bacterium, highlighting the need to develop and optimize immunocompetent in vitro models.

bacterial genotoxin, bacteria, DNA damage response, organotypic model, immune cells.
National Category
Cell Biology Immunology
Research subject
biology; cell research; Immunology
urn:nbn:se:umu:diva-203903 (URN)
Available from: 2023-01-23 Created: 2023-01-23 Last updated: 2023-01-24

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