Publications by authors named "N G Gratz"

Neuraminidase A (NanA) is an important virulence factor that is anchored to the pneumococcal cell wall and cleaves sialic acid on host substrates. We noted that a secreted allele of NanA was over-represented in invasive pneumococcal isolates and promoted the development of meningitis when swapped into the genome of non-meningitis isolates replacing cell wall-anchored NanA. Both forms of recombinant NanA directly activated transforming growth factor (TGF)-β, increased SMAD signalling and promoted loss of endothelial tight junction ZO-1.

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Protective responses against pathogens require a rapid mobilization of resting neutrophils and the timely removal of activated ones. Neutrophils are exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged neutrophils is regulated differently from that in the circulating steady-state pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated infiltrating murine neutrophils but not neutrophil cellularity.

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Article Synopsis
  • Pathogen clearance and host resilience to infections are both essential for survival, with myeloid cells like neutrophils and macrophages playing key roles in immune response and pathogen elimination.
  • Excessive inflammation from poorly regulated myeloid cells can hinder host resilience, and programmed cell death (PCD) serves as a mechanism to control inflammation and balance immune responses.
  • Research using a mouse model with decreased myeloid cell death showed that while this reduced inflammation and boosted host resilience, it had little effect on the actual clearance of bacterial pathogens like Legionella pneumophila and Streptococcus pyogenes.
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Bacterial meningitis is a devastating disease occurring worldwide with up to half of the survivors left with permanent neurological sequelae. Due to intrinsic properties of the meningeal pathogens and the host responses they induce, infection can cause relatively specific lesions and clinical syndromes that result from interference with the function of the affected nervous system tissue. Pathogenesis is based on complex host-pathogen interactions, some of which are specific for certain bacteria, whereas others are shared among different pathogens.

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