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James R. Lokensgard - One of the best experts on this subject based on the ideXlab platform.

  • Infiltrating Regulatory B Cells Control Neuroinflammation following Viral Brain Infection
    Journal of immunology (Baltimore Md. : 1950), 2014
    Co-Authors: Manohar B Mutnal, Scott J. Schachtele, James R. Lokensgard
    Abstract:

    Previous studies have demonstrated the existence of a subset of B lymphocytes, regulatory B cells (Bregs), which modulate immune function. In this study, in vivo and in vitro experiments were undertaken to elucidate the role of these Bregs in controlling neuroinflammation following viral Brain Infection. We used multicolor flow cytometry to phenotype lymphocyte subpopulations infiltrating the Brain, along with in vitro cocultures to assess their anti-inflammatory and immunoregulatory roles. This distinctive subset of CD19+CD1dhiCD5+ B cells was found to infiltrate the Brains of chronically infected animals, reaching highest levels at the latest time point tested (30 d postInfection). B cell–deficient Jh−/− mice were found to develop exacerbated neuroimmune responses as measured by enhanced accumulation and/or retention of CD8+ T cells within the Brain, as well as increased levels of microglial activation (MHC class II). Conversely, levels of Foxp3+ regulatory T cells were found to be significantly lower in Jh−/− mice when compared with wild-type (Wt) animals. Further experiments showed that in vitro–generated IL-10–secreting Bregs (B10) were able to inhibit cytokine responses from microglia following stimulation with viral Ags. These in vitro–generated B10 cells were also found to promote proliferation of regulatory T cells in coculture studies. Finally, gain-of-function experiments demonstrated that reconstitution of Wt B cells into Jh−/− mice restored neuroimmune responses to levels exhibited by infected Wt mice. Taken together, these results demonstrate that Bregs modulate T lymphocyte as well as microglial cell responses within the infected Brain and promote CD4+Foxp3+ T cell proliferation in vitro.

  • Reactive oxygen species drive herpes simplex virus (HSV)-1-induced proinflammatory cytokine production by murine microglia
    Journal of Neuroinflammation, 2011
    Co-Authors: Shuxian Hu, Scott J. Schachtele, Wen S. Sheng, James R. Lokensgard
    Abstract:

    Background Production of reactive oxygen species (ROS) and proinflammatory cytokines by microglial cells in response to viral Brain Infection contributes to both pathogen clearance and neuronal damage. In the present study, we examined the effect of herpes simplex virus (HSV)-1-induced, NADPH oxidase-derived ROS in activating mitogen-activated protein kinases (MAPKs) as well as driving cytokine and chemokine expression in primary murine microglia.

  • Memory T cells persisting in the Brain following MCMV Infection induce long-term microglial activation via interferon-γ
    Journal of NeuroVirology, 2011
    Co-Authors: Manohar B Mutnal, Morgan R Little, James R. Lokensgard
    Abstract:

    Murine cytomegalovirus (MCMV) Brain Infection stimulates microglial cell-driven proinflammatory chemokine production which precedes the presence of Brain-infiltrating systemic immune cells. Here, we show that in response to MCMV Brain Infection, antigen-specific CD8(+) T cells migrated into the Brain and persisted as long-lived memory cells. The role of these persistent T cells in the Brain is unclear because most of our understanding of antimicrobial T cell responses comes from analyses of lymphoid tissue. Strikingly, memory T cells isolated from the Brain exhibited an effector phenotype and produced IFN-γ upon restimulation with viral peptide. Furthermore, we observed time-dependent and long-term activation of resident microglia, indicated by chronic MHC class II up-regulation and TNF-α production. The immune response in this immunologically restricted site persisted in the absence of active viral replication. Lymphocyte infiltrates were detected until 30 days post-Infection (p.i.), with CD8(+) and CD4(+) T cells present at a 3:1 ratio, respectively. We then investigated the role of IFN-γ in chronic microglial activation by using IFN-γ-knockout (GKO) mice. At 30 days p.i., GKO mice demonstrated a similar phenotypic Brain infiltrate when compared to wild-type mice (Wt), however, MHC class II expression on microglia isolated from these GKO mice was significantly lower compared to Wt animals. When IFN-γ producing CD8(+) T cells were reconstituted in GKO mice, MHC class II up-regulation on microglial cells was restored. Taken together, these results suggest that MCMV Brain Infection results in long-term persistence of antigen-specific CD8(+) T cells which produce IFN-γ and drive chronic microglial cell activation. This response was found to be dependent on IFN-γ production by viral Ag-specific T cells during the chronic phase of disease.

  • Murine Cytomegalovirus Infection of Neural Stem Cells Alters Neurogenesis in the Developing Brain
    PloS one, 2011
    Co-Authors: Manohar B Mutnal, Maxim C-j Cheeran, James R. Lokensgard
    Abstract:

    Background Congenital cytomegalovirus (CMV) Brain Infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal Brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital Brain Infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV) and the pattern of injury to the developing Brain.

  • Excess neutrophil infiltration during cytomegalovirus Brain Infection of interleukin-10-deficient mice.
    Journal of neuroimmunology, 2010
    Co-Authors: Manohar B Mutnal, Maxim C-j Cheeran, Morgan R Little, James R. Lokensgard
    Abstract:

    Wild-type mice control murine cytomegalovirus (MCMV) Brain Infection, but identical Infection is lethal to animals deficient in interleukin (IL)-10. Here, we report that MCMV-infected IL-10 knockout (KO) mice displayed a marked increase in neutrophil infiltration into the infected, IL-10-deficient Brain when compared to wild-type animals. Enhanced microglial cell activation, determined by MHC class II up-regulation, overexpression of CXCL2, and elevated P-selectin mRNA levels were observed. In vivo blocking of CXCL2 attenuated neutrophil infiltration and significantly improved the outcome of Infection. Collectively, these data indicate that the absence of IL-10 results in pathologic neutrophil infiltration into MCMV-infected Brains.

L Svensson - One of the best experts on this subject based on the ideXlab platform.

  • Neonatal herpes simplex virus type 1 Brain Infection affects the development of sensorimotor gating in rats.
    Brain research, 2000
    Co-Authors: J A Engel, J Zhang, T Bergström, N Conradi, C Forkstam, A Liljeroth, L Svensson
    Abstract:

    The effect of neonatal Brain Infection of herpes simplex virus type 1 (HSV-1) on the development of sensorimotor function in the rat was investigated using an acoustic startle paradigm. Intracerebral inoculation of HSV-1 at day 2 after birth, but not at day 4, caused a significant delay in the development of prepulse inhibition of acoustic startle. A decrease in prepulse inhibition was shown at 37, 46 and 58 days of age in these rats compared to control rats. No evidence was obtained for other behavioural dysfunctions such as differences in sensorimotor reactivity, sensorimotor response habituation, spontaneous locomotor activity, rearing activity or stereotyped behaviour. Prepulse inhibition of acoustic startle is an accepted model of sensorimotor gating in the CNS, a function which has been shown diminished in schizophrenic persons. The present results suggest that early viral Infections during a neurone-susceptible period may contribute to the development of this deficit.

Sven Bergström - One of the best experts on this subject based on the ideXlab platform.

  • Residual Brain Infection in murine relapsing fever borreliosis can be successfully treated with ceftriaxone.
    Microbial pathogenesis, 2007
    Co-Authors: Christer Larsson, Jenny Lundqvist, Sven Bergström
    Abstract:

    Like several other spirochetes, relapsing fever Borrelia can cause persistent Infection of the central nervous system (CNS). By treating mice harboring residual Borrelia duttonii Brain Infection wi ...

  • Persistent Brain Infection and disease reactivation in relapsing fever borreliosis.
    Microbes and infection, 2006
    Co-Authors: Christer Larsson, Marie Andersson, Jenni Pelkonen, Betty P. Guo, Annika Nordstrand, Sven Bergström
    Abstract:

    Relapsing fever, an Infection caused by Borrelia spirochetes, is generally considered a transient, self-limiting disease in humans. The present study reveals that murine Infection by Borrelia duttonii can be reactivated after an extended time as a silent Infection in the Brain, with no bacteria appearing in the blood and spirochete load comparable to the numbers in an infected tick. The host cerebral gene expression pattern is indistinguishable from that of uninfected animals, indicating that persistent bacteria are not recognized by the immune system nor cause noticeable tissue damage. Silent Infection can be reactivated by immunosuppression, inducing spirochetemia comparable to that of initial densities. B. duttonii has never been found in any host except man and the tick vector. We therefore propose the Brain to be a possible natural reservoir of the spirochete. The view of relapsing fever as an acute disease should be extended to include in some cases prolonged persistence, a feature characteristic of the related spirochetal Infections Lyme disease and syphilis.

Catherine L. Lawson - One of the best experts on this subject based on the ideXlab platform.

  • Residual Brain Infection in Relapsing-Fever Borreliosis
    The Journal of infectious diseases, 2006
    Co-Authors: Diego Cadavid, Marie Sondey, Edwin Garcia, Catherine L. Lawson
    Abstract:

    Background. Neurological involvement is common in the spirochetal Infection relapsing fever (RF) in both humans and experimental animals. RF is best known for antigenic variation caused by the sequential expression of variable outer membrane lipoproteins of 2 sizes, variable small (Vsp) and variable large (Vlp) proteins. Less understood is the persistence of RF borreliae in the Brain after they are cleared from the blood, referred to as residual Brain Infection (RBI). Our goal was to investigate the phenomenon of RBI in RF. Methods. We studied RBI in immunocompetent mice by culturing blood and perfused Brain samples 1 month after intraperitoneal inoculation with Borrelia turicatae serotype 1 (Btl). Mice deficient in Toll-like receptor 2 (TLR2 -/- ) or in B and T cells (scid) were included for comparison. Results. All scid mice had persistent Infection in blood and Brain. RBI was found in 3 (19%) of 16 immunocompetent and TLR2 -/- mice. RBI was caused by either persistence of the original serotype (Btl) or newly emerged Vsp (n = 1, renamed Bt3) or Vlp serotypes. The Vsp of Btl (Vspl) and Bt3 (Vsp3) were 75% identical. Conclusions. RBI in RF is relatively frequent and can occur by persistence of the original or newly emerged serotypes.

Katarzyna Bilinska - One of the best experts on this subject based on the ideXlab platform.

  • sars cov 2 olfaction Brain Infection and the urgent need for clinical samples allowing earlier virus detection
    ACS Chemical Neuroscience, 2020
    Co-Authors: Rafal Butowt, Katarzyna Bilinska
    Abstract:

    The novel SARS-CoV-2 virus has very high infectivity, which allows it to spread rapidly around the world. Attempts at slowing the pandemic at this stage depend on the number and quality of diagnostic tests performed. We propose that the olfactory epithelium from the nasal cavity may be a more appropriate tissue for detection of SARS-CoV-2 virus at the earliest stages, prior to onset of symptoms or even in asymptomatic people, as compared to commonly used sputum or nasopharyngeal swabs. Here we emphasize that the nasal cavity olfactory epithelium is the likely site of enhanced binding of SARS-CoV-2. Multiple non-neuronal cell types present in the olfactory epithelium express two host receptors, ACE2 and TMPRSS2 proteases, that facilitate SARS-CoV-2 binding, replication, and accumulation. This may be the underlying mechanism for the recently reported cases of smell dysfunction in patients with COVID-19. Moreover, the possibility of subsequent Brain Infection should be considered which begins in olfactory neurons. In addition, we discuss the possibility that olfactory receptor neurons may initiate rapid immune responses at early stages of the disease. We emphasize the need to undertake research focused on additional aspects of SARS-CoV-2 actions in the nervous system, especially in the olfactory pathway.