Recovery from an acute systemic and central LPS-inflammation challenge is affected by mouse sex and genetic background

Meneses, Gabriela; Rosetti, M.; Espinosa, Alejandro; Florentino, A.; Bautista, M.; Díaz, Georgina; Olvera, Guillermo; Bárcena, Brandon; Fleury, Agnès; Adalid‐Peralta, Laura; Lamoyi, Edmundo; Fragoso, Gladis; Sciutto, Edda

doi:10.1371/journal.pone.0201375

Cited by 35 publications

(25 citation statements)

References 36 publications

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“…Our study differed from these previous reports as we utilized: (a) a different dose of LPS; (b) mice of both sexes; and (c) transgenic mice on a mixed genetic background. As the effects of systemic LPS on microglia activation in mice are dependent on genetic background and sex (Meneses et al, ), these factors may explain the differences between these studies.…”

Section: Discussionmentioning

confidence: 99%

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Dando

Kazanis

Chinnery

et al. 2018

Glia

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The central nervous system (CNS) is considered to be immune privileged, owing in part to the absence of major histocompatibility (MHC) class II + cells in the healthy brain parenchyma. However, systemic inflammation can activate microglia to express MHC class II, suggesting that systemic inflammation may be sufficient to mature microglia into functional antigen presenting cells (APCs). We examined the effects of systemic lipopolysaccharide (LPS)-induced inflammation on the phenotype and function of putative APCs within the mouse brain parenchyma, as well as its supporting tissues-the choroid plexus and meninges. Microglia isolated from different regions of the brain demonstrated significant heterogeneity in their ability to present antigen to naïve OT-II CD4 + T cells following exposure to systemic LPS. Olfactory bulb microglia (but not cortical microglia) intimately interacted with T cells in vivo and stimulated T cell proliferation in vitro, albeit in the absence of co-stimulation. In contrast, myeloid cells within the choroid plexus and meninges were immunogenic and upregulated the co-stimulatory molecule CD80 following systemic inflammation. Dural APCs, which clustered around LYVE-1 + lymphatics, were more efficient at stimulating naïve T cell proliferation than choroid plexus APCs, suggesting that the dura may be an underappreciated site for immune interactions. This study has highlighted the functional diversity of myeloid cells within the sub-compartments of the CNS and its supporting tissues. Furthermore, these findings demonstrate that systemic inflammation can mature selected microglia populations and choroid plexus/meningeal myeloid cells into functional APCs, which may contribute to the pathogenesis of neuroinflammation and neurodegenerative diseases. K E Y W O R D Santigen presenting cells, brain parenchyma, central nervous system, meninges, microglia

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Section: Discussionmentioning

confidence: 99%

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Dando

Kazanis

Chinnery

et al. 2018

Glia

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“…Next, we wondered how the cytokine profile in response to 40 Hz flicker differed from acute inflammation. Thus, we assessed cytokine expression in the visual cortex of animals intraperitoneally injected with LPS, a traditional, acute model of inflammation (Gabellec et al, 1995;Qin et al, 2007;Meneses et al, 2018). As in our flicker experiments, we characterized cytokine expression in visual cortex of mice injected with LPS versus vehicle injection and separated these differences using a PLSDA (Fig.…”

Section: Hz Flicker Induces Neuroimmune Profile Distinct From Acute Imentioning

confidence: 99%

Gamma Visual Stimulation Induces a Neuroimmune Signaling Profile Distinct from Acute Neuroinflammation

et al. 2019

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Many neurodegenerative and neurological diseases are rooted in dysfunction of the neuroimmune system; therefore, manipulating this system has strong therapeutic potential. Prior work has shown that exposing mice to flickering lights at 40 Hz drives gamma frequency (ϳ40 Hz) neural activity and recruits microglia, the primary immune cells of the brain, revealing a novel method to manipulate the neuroimmune system. However, the biochemical signaling mechanisms between 40 Hz neural activity and immune recruitment remain unknown. Here, we exposed wild-type male mice to 5-60 min of 40 Hz or control flicker and assessed cytokine and phosphoprotein networks known to play a role in immune function. We found that 40 Hz flicker leads to increases in the expression of cytokines which promote microglial phagocytic states, such as IL-6 and IL-4, and increased expression of microglial chemokines, such as macrophagecolony-stimulating factor and monokine induced by interferon-␥. Interestingly, cytokine effects differed as a function of stimulation frequency, revealing a range of neuroimmune effects of stimulation. To identify possible mechanisms underlying cytokine expression, we quantified the effect of the flicker on intracellular signaling pathways known to regulate cytokine levels. We found that a 40 Hz flicker upregulates phospho-signaling within the nuclear factor-light-chain-enhancer of activated B cells (NF-B) and mitogen-activated protein kinase (MAPK) pathways. While cytokine expression increased after 1 h of 40 Hz flicker stimulation, protein phosphorylation in the NF-B pathway was upregulated within minutes. Importantly, the cytokine expression profile induced by 40 Hz flicker was different from cytokine changes in response to acute neuroinflammation induced by lipopolysaccharides. These results are the first, to our knowledge, to show how visual stimulation rapidly induces critical neuroimmune signaling in healthy animals.

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“…Prior sepsis alters the responsivity of the circadian system to subsequent immune challenges. LPS-induced sepsis shapes the response to subsequent administration of lower dosages of LPS in mice (Meneses et al, 2018). Testing the responsiveness of the circadian system of mice to LPS showed that while in control animals LPS induced a significant phase delay of the behavioral rhythm, it did not occur in post-septic animals (Castanon-Cervantes et al, 2010).…”

Section: The Circadian Rhythm Plays a Role In The Pathogenesis Of Sepsismentioning

confidence: 99%

A Personalized Signature and Chronotherapy-Based Platform for Improving the Efficacy of Sepsis Treatment

Kenig

Ilan

2019

Front. Physiol.

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Sepsis remains a major therapeutic challenge and is associated with a high rate of morbidity and mortality. It is a dynamic condition in which multiple parameters change over time, rendering it difficult to overcome the various injurious responses, which worsen the prognosis in these patients. The prognosis of sepsis is associated with a disbalance of compensatory responses to infectious triggers, part of which can be deleterious. Marked inter-and intra-patient variability characterizes the mechanisms that underlie sepsis progression and determine the response to therapy. In this paper, we review some of the data on the use of chronopharmacological approaches for the treatment of patients with sepsis and discuss the role of the autonomic nervous system in the mechanisms associated with immune response and chronotherapy in these patients. We describe the implementation of an individualized platform that is based on the personalized autonomic nervous system, immune, and chronobiologyderived parameters for generating a patient-tailored therapeutic regimen. The notion of overcoming the deleterious compensatory response in a highly dynamic system in sepsis is presented to ensure an improved response to current therapies.

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Recovery from an acute systemic and central LPS-inflammation challenge is affected by mouse sex and genetic background

Cited by 35 publications

References 36 publications

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Gamma Visual Stimulation Induces a Neuroimmune Signaling Profile Distinct from Acute Neuroinflammation

A Personalized Signature and Chronotherapy-Based Platform for Improving the Efficacy of Sepsis Treatment

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