Pneumococcal Peptidoglycan-Polysaccharides Regulate Toll-Like Receptor 2 in the Mouse Middle Ear Epithelial Cells

Komori, Masahiro; Nakamura, Yoshihisa; Ping, Jesse; Ling, Feng; Toyama, Katsuhiro; Kim, Youngki; Ferrieri, Patricia; Lin, Jizhen

doi:10.1203/pdr.0b013e3182055237

Cited by 37 publications

(47 citation statements)

References 26 publications

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“…[23] , was used to investigate possible combinatorial effects of TLR signaling and the vitamin D pathway. Vitamin D-stimulated neutrophils showed a significantly higher killing of the serotype 4 strain T4, its isogenic mutant in the capsule, T4R ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Promotes Pneumococcal Killing and Modulates Inflammatory Responses in Primary Human Neutrophils

2017

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Streptococcus pneumoniae is a major human pathogen and a leading cause of pneumonia, septicemia, and meningitis worldwide. Despite clinical studies linking vitamin D deficiency and pneumonia, molecular mechanisms behind these observations remain unclear. In particular, the effects of vitamin D on neutrophil responses remain unknown. Using pneumococcal strains, primary neutrophils isolated from human blood, and sera from patients with frequent respiratory tract infections (RTIs), we investigated the effects of vitamin D on neutrophil bactericidal and inflammatory responses, including pattern recognition receptors, antimicrobial peptides, and cytokine regulation. We found that vitamin D upregulated pattern recognition receptors, TLR2, and NOD2, and induced the antimicrobial human neutrophil peptides (HNP1-3) and LL-37, resulting in increased killing of pneumococci in a vitamin D receptor-dependent manner. Antibodies targeting HNP1-3 inhibited bacterial killing. Vitamin D supplementation of serum from patients with bacterial RTIs enhanced neutrophil killing. Moreover, vitamin D lowered inflammatory cytokine production by infected neutrophils via IL-4 production and the induction of suppressor of cytokine signaling (SOCS) proteins SOCS-1 and SOCS-3, leading to the suppression of NF-κB signaling. Thus, vitamin D enhances neutrophil killing of S. pneumoniae while dampening excessive inflammatory responses and apoptosis, suggesting that vitamin D could be used alongside antibiotics when treating pneumococcal infections.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Promotes Pneumococcal Killing and Modulates Inflammatory Responses in Primary Human Neutrophils

2017

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“…The latter requires several brain areas to be connected and is built upon combinations of previously acquired components of simple social behaviors. Even more sophisticated social behaviors, such as empathy and theory of mind, develop by middle childhood (Happe and Frith, 2014; Korkmaz, 2011). Social communication skills are gradually acquired along these maturation processes.…”

Section: Neurobiological Framework For Cognitive Functions: Functimentioning

confidence: 99%

Converging models of schizophrenia – Network alterations of prefrontal cortex underlying cognitive impairments

Sakurai

Gamo

Hikida

et al. 2015

Progress in Neurobiology

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The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal.

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“…Some of these cytokines and inflammatory mediators such as IFNγ and interleukin-6 (IL-6) are critical for COM because they are involved in the regulation of immune and inflammatory responses. They include IFNγ, TNFα [50], IL-6, interleukin-10 (IL-10) [51] and VEGF. IFNγ is a major immune interferon [52] and now is known as an potent regulator for the expression of PD-L1.…”

Section: Important Inflammatory Cytokines and Mediators In Ommentioning

confidence: 99%

Adaptive Immunity in the Middle Ear Mucosa with Chronic Otitis Media

Lin¹,

Zhao²

2014

Int J Otorhinolaryngol

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Pneumococcal Peptidoglycan-Polysaccharides Regulate Toll-Like Receptor 2 in the Mouse Middle Ear Epithelial Cells

Cited by 37 publications

References 26 publications

Vitamin D Promotes Pneumococcal Killing and Modulates Inflammatory Responses in Primary Human Neutrophils

Vitamin D Promotes Pneumococcal Killing and Modulates Inflammatory Responses in Primary Human Neutrophils

Converging models of schizophrenia – Network alterations of prefrontal cortex underlying cognitive impairments

Adaptive Immunity in the Middle Ear Mucosa with Chronic Otitis Media

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