Dataset Information

CX3CR1⁺ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α.

ABSTRACT: Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor cortex using two-photon microscopy. We found that peripheral immune activation caused dendritic spine loss, impairments in learning-dependent dendritic spine formation and deficits in multiple learning tasks in mice. These observed synaptic alterations in the cortex were mediated by peripheral-monocyte-derived cells and did not require microglial function in the central nervous system. Furthermore, activation of CX3CR1^highLy6C^low monocytes impaired motor learning and learning-related dendritic spine plasticity through tumor necrosis factor (TNF)-α-dependent mechanisms. Taken together, our results highlight CX3CR1^high monocytes and TNF-α as potential therapeutic targets for preventing infection-induced cognitive dysfunction.

SUBMITTER: Garre JM

PROVIDER: S-EPMC5590232 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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CX3CR1<sup>+</sup> monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α.

Garré Juan Mauricio JM Silva Hernandez Moura HM Lafaille Juan J JJ Yang Guang G

Nature medicine 20170515 6

Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor ...[more]

PMID: 28504723

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Project description:HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14++CD16+ monocytes were found to accumulate and CD11c+ conventional dendritic cells (cDC) to be depleted in a Portuguese cohort of people living with HIV-2 (PLWHIV-2), compared to blood bank healthy donors (HD). We studied more precisely classical monocytes; CD16+ inflammatory (intermediate, non-classical and slan+ monocytes, known to accumulate during viremic HIV-1 infection); cDC1, important for cross-presentation, and cDC2, both depleted during HIV-1 infection. We analyzed by flow cytometry these PBMC subsets from Paris area residents: 29 asymptomatic, untreated PLWHIV-2 from the IMMUNOVIR-2 study, part of the ANRS-CO5 HIV-2 cohort: 19 long-term non-progressors (LTNP; infection ≥8 years, undetectable viral load, stable CD4 counts≥500/μL; 17 of West-African origin -WA), and 10 non-LTNP (P; progressive infection; 9 WA); and 30 age-and sex-matched controls: 16 blood bank HD with unknown geographical origin, and 10 HD of WA origin (GeoHD). We measured plasma bacterial translocation markers by ELISA. Non-classical monocyte counts were higher in GeoHD than in HD (54 vs. 32 cells/μL, p = 0.0002). Slan+ monocyte counts were twice as high in GeoHD than in HD (WA: 28 vs. 13 cells/μL, p = 0.0002). Thus cell counts were compared only between participants of WA origin. They were similar in LTNP, P and GeoHD, indicating that there were no HIV-2 related differences. cDC counts did not show major differences between the groups. Interestingly, inflammatory monocyte counts correlated with plasma sCD14 and LBP only in PLWHIV-2, especially LTNP, and not in GeoHD. In conclusion, in LTNP PLWHIV-2, inflammatory monocyte counts correlated with LBP or sCD14 plasma levels, indicating a potential innate immune response to subclinical bacterial translocation. As GeoHD had higher inflammatory monocyte counts than HD, our data also show that specific controls are important to refine innate immunity studies.

Dataset Information

CX3CR1⁺ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α.

Publications

CX3CR1<sup>+</sup> monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α.

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Dataset Information

CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α.

Publications

CX3CR1<sup>+</sup> monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

CX3CR1⁺ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α.