Streptococcus pneumoniae infection regulates expression of neurotrophic factors in the olfactory bulb and cultured olfactory ensheathing cells

Mendoza, Susana Ruiz; Macedo-Ramos, Hugo; Santos, Fernanda A. dos; Quadros-de-Souza, L.C.; Paiva, Mauricio M.; Pinto, Tatiana Castro Abreu; Teixeira, Lúcia Martins; Baetas‐da‐Cruz, Wagner

doi:10.1016/j.neuroscience.2016.01.016

Cited by 14 publications

(14 citation statements)

References 45 publications

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“…Some evidence points to a non-hematogenous invasion of the brain by S. pneumoniae, through transport along the olfactory bulb (OB)10. Recent data from our group confirmed these findings, by detecting S. pneumoniae DNA in the OB of bacteria-challenged mice11. Although several lines of evidence indicate that S. pneumoniae reaches the OB, based on the use of molecular techniques for the detection of bacterial DNA and specific pneumococcal antigens, no data are available to support the idea that the bacteria can survive in the OB cells and therefore be able to spread the infection through the CNS.…”

supporting

confidence: 63%

“…Collectively, these data suggest a possible mechanism triggered by S. pneumoniae that is able to suppress the pathway for expression of iNOS and therefore the production of NO. Furthermore, recent data from our group suggest the existence of a soluble factor that is generated after interaction of S. pneumoniae with OECs, which can simultaneously be able to regulate NF-κB activation and the viability of microglia11. However, continued studies are necessary to better understand the influences of S. pneumoniae on the biosynthetic pathway for NO production, and its impact on continuous NF-κB p65 activation in OECs.…”

Section: Discussionmentioning

confidence: 99%

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Streptococcus pneumoniae resists intracellular killing by olfactory ensheathing cells but not by microglia

Macedo-Ramos

Mendoza

Mariante

et al. 2016

Sci Rep

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Olfactory ensheathing cells (OECs) are a type of specialized glial cell currently considered as having a double function in the nervous system: one regenerative, and another immune. Streptococcus pneumoniae is a major agent of severe infections in humans, including meningitis. It is commonly found in the nasopharynx of asymptomatic carriers, and, under certain still unknown conditions, can invade the brain. We evaluated whether pneumococcal cells recovered from lysed OECs and microglia are able to survive by manipulating the host cell activation. An intracellular-survival assay of S. pneumoniae in OECs showed a significant number of bacterial CFU recovered after 3 h of infection. In contrast, microglia assays resulted in a reduced number of CFU. Electron-microscopy analysis revealed a large number of pneumococci with apparently intact morphology. However, microglia cells showed endocytic vesicles containing only bacterial cell debris. Infection of OEC cultures resulted in continuous NF-κB activation. The IFN-γ-induced increase of iNOS expression was reversed in infected OECs. OECs are susceptible to S. pneumoniae infection, which can suppress their cytotoxic mechanisms in order to survive. We suggest that, in contrast to microglia, OECs might serve as safe targets for pneumococci, providing a more stable environment for evasion of the immune system.

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supporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Streptococcus pneumoniae resists intracellular killing by olfactory ensheathing cells but not by microglia

Macedo-Ramos

Mendoza

Mariante

et al. 2016

Sci Rep

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“…Additionally, the analysis of nasal samples from grass-pollen allergic patients receiving allergen-specific immunotherapy shows the downregulation of the expression of GFLs and their receptors versus untreated patients [82]. Finally, in another context, the infection with the bacterium Streptococcus pneumoniae, causing diseases such as pneumonia, sinusitis and meningitis, alters the expression level of GDNF in the olfactory bulb, which could indirectly influence microglial activation [83].…”

Section: In Asthma and Allergic Rhinitismentioning

confidence: 99%

Revisiting the Role of Neurotrophic Factors in Inflammation

Morel

Domingues

Zimmer

et al. 2020

Cells

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The neurotrophic factors are well known for their implication in the growth and the survival of the central, sensory, enteric and parasympathetic nervous systems. Due to these properties, neurturin (NRTN) and Glial cell-derived neurotrophic factor (GDNF), which belong to the GDNF family ligands (GFLs), have been assessed in clinical trials as a treatment for neurodegenerative diseases like Parkinson’s disease. In addition, studies in favor of a functional role for GFLs outside the nervous system are accumulating. Thus, GFLs are present in several peripheral tissues, including digestive, respiratory, hematopoietic and urogenital systems, heart, blood, muscles and skin. More precisely, recent data have highlighted that different types of immune and epithelial cells (macrophages, T cells, such as, for example, mucosal-associated invariant T (MAIT) cells, innate lymphoid cells (ILC) 3, dendritic cells, mast cells, monocytes, bronchial epithelial cells, keratinocytes) have the capacity to release GFLs and express their receptors, leading to the participation in the repair of epithelial barrier damage after inflammation. Some of these mechanisms pass on to ILCs to produce cytokines (such as IL-22) that can impact gut microbiota. In addition, there are indications that NRTN could be used in the treatment of inflammatory airway diseases and it prevents the development of hyperglycemia in the diabetic rat model. On the other hand, it is suspected that the dysregulation of GFLs produces oncogenic effects. This review proposes the discussion of the biological understanding and the potential new opportunities of the GFLs, in the perspective of developing new treatments within a broad range of human diseases.

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“…This result plus the concurrent infection of the nasopharynx and sinus tissue suggest a cascade of events that can lead to invasion and possibly that the severity of the sinus infection is a precursor to CNS invasion. This, along with recent evidence of the association and manipulation of the olfactory ensheathing cells by pneumococci (48,49), provides credence to the idea that the olfactory nerves are the portals of entry into the CNS.…”

Section: Discussionmentioning

confidence: 56%

Free Sialic Acid Acts as a Signal That Promotes Streptococcus pneumoniae Invasion of Nasal Tissue and Nonhematogenous Invasion of the Central Nervous System

2016

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Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial meningitis and neurological sequelae in children worldwide. Acute bacterial meningitis is widely considered to result from bacteremia that leads to blood-brain barrier breakdown and bacterial dissemination throughout the central nervous system (CNS). Previously, we showed that pneumococci can gain access to the CNS through a nonhematogenous route without peripheral blood infection. This access is thought to occur when the pneumococci in the upper sinus follow the olfactory nerves and enter the CNS through the olfactory bulbs. In this study, we determined whether the addition of exogenous sialic acid postcolonization promotes nonhematogenous invasion of the CNS. Previously, others showed that treatment with exogenous sialic acid post-pneumococcal infection increased the numbers of CFU recovered from an intranasal mouse model of infection. Using a pneumococcal colonization model, an in vivo imaging system, and a multiplex assay for cytokine expression, we demonstrated that sialic acid can increase the number of pneumococci recovered from the olfactory bulbs and brains of infected animals. We also show that pneumococci primarily localize to the olfactory bulb, leading to increased expression levels of proinflammatory cytokines and chemokines. These findings provide evidence that sialic acid can enhance the ability of pneumococci to disseminate into the CNS and provide details about the environment needed to establish nonhematogenous pneumococcal meningitis. Streptococcus pneumoniae (pneumococcus) is a common asymptomatic colonizer of the nasopharynx of healthy individuals. Colonization can occur at any point during a person's life but occurs most frequently in the first few years of life, with colonization rates of 50% to 70% in hosts Յ3 years of age (1). Colonization in the young and elderly can lead to bacterial pneumonia, otitis media, meningitis, and sepsis, with approximately 4 million new cases of illness and 22,000 deaths annually in the United States (2). Pneumococcal meningitis is traditionally thought to be established when bacteria disseminate into the lower respiratory tract and cause a focal pneumonia, which is proceeded by septicemia and subsequent crossing of the blood-brain barrier (3-5). We and others have shown that pneumococci and other pathogens have the ability to invade the central nervous system (CNS) through a nonhematogenous route after nasopharynx colonization. However, further research is needed to understand conditions that may contribute to CNS dissemination (6-11).Clinically, there have been cases of bacterial meningitis reported in the absence of a positive blood culture. A study of child cerebral malaria in Kenyan children found that of 29 cases of acute bacterial meningitis, 10 cases had negative blood cultures but positive cerebrospinal fluid (CSF) samples, and half of these infections were caused by Streptococcus pneumoniae (12). A 2005 study of neonatal meningitis found that 38% of cases of confirmed bacteria...

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Streptococcus pneumoniae infection regulates expression of neurotrophic factors in the olfactory bulb and cultured olfactory ensheathing cells

Cited by 14 publications

References 45 publications

Streptococcus pneumoniae resists intracellular killing by olfactory ensheathing cells but not by microglia

Streptococcus pneumoniae resists intracellular killing by olfactory ensheathing cells but not by microglia

Revisiting the Role of Neurotrophic Factors in Inflammation

Free Sialic Acid Acts as a Signal That Promotes Streptococcus pneumoniae Invasion of Nasal Tissue and Nonhematogenous Invasion of the Central Nervous System

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