L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis.

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome.

Novel Mouse Model Reveals That Serine Phosphorylation of L-Plastin Is Essential for Effective Splenic Clearance of Pneumococcus.

Asplenia imparts susceptibility to life-threatening sepsis with encapsulated bacteria, such as the pneumococcus. However, the cellular components within the splenic environment that guard against pneumococcal bacteremia have not been defined. The actin-bundling protein L-plastin (LPL) is essential for the generation of marginal zone B cells and for anti-pneumococcal host defense, as revealed by a mouse model of genetic LPL deficiency.

Inhaled GM-CSF in neonatal mice provides durable protection against bacterial pneumonia.

Pneumonia poses profound health threats to preterm infants. Alveolar macrophages (AMs) eliminate inhaled pathogens while maintaining surfactant homeostasis. As AM development only occurs perinatally, therapies that accelerate AM maturation in preterms may improve outcomes.

LRRK1 regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L-plastin.

Mice with disruption of Lrrk1 and patients with nonfunctional mutant Lrrk1 exhibit severe osteopetrosis phenotypes because of osteoclast cytoskeletal dysfunction. To understand how Lrrk1 regulates osteoclast function by modulating cytoskeleton rearrangement, we examined the proteins that are differentially phosphorylated in wild-type mice and Lrrk1-deficient osteoclasts by metal affinity purification coupled liquid chromatography/mass spectrometry (LC/MS) analyses. One of the candidates that we identified by LC/MS is L-plastin, an actin bundling protein.

Colonization with 19F and other pneumococcal conjugate vaccine serotypes in children in St. Louis, Missouri, USA.

Background: The epidemiology of nasopharyngeal (NP) pneumococcal carriage varies with geography and has changed in response to pneumococcal conjugate vaccine (PCV): a low prevalence (3% or less of colonizing isolates) of colonization by vaccine-type (VT) pneumococcal serotypes after PCV introduction has been reported. The primary goal of this study was to determine the VT serotype prevalence of NP pneumococcal colonization of children residing in the St. Louis, MO, USA metropolitan area following introduction of the 13-valent PCV in 2010.

Alveolar macrophage development in mice requires L-plastin for cellular localization in alveoli.

Alveolar macrophages are lung-resident sentinel cells that develop perinatally and protect against pulmonary infection. Molecular mechanisms controlling alveolar macrophage generation have not been fully defined. Here, we show that the actin-bundling protein L-plastin (LPL) is required for the perinatal development of alveolar macrophages.

L-Plastin promotes podosome longevity and supports macrophage motility.

Elucidating the molecular regulation of macrophage migration is essential for understanding the pathophysiology of multiple human diseases, including host responses to infection and autoimmune disorders. Macrophage migration is supported by dynamic rearrangements of the actin cytoskeleton, with formation of actin-based structures such as podosomes and lamellipodia. Here we provide novel insights into the function of the actin-bundling protein l-plastin (LPL) in primary macrophages.

Mst1 Kinase Regulates the Actin-Bundling Protein L-Plastin To Promote T Cell Migration.

Exploring the mechanisms controlling lymphocyte trafficking is essential for understanding the function of the immune system and the pathophysiology of immunodeficiencies. The mammalian Ste20-like kinase 1 (Mst1) has been identified as a critical signaling mediator of T cell migration, and loss of Mst1 results in immunodeficiency disease. Although Mst1 is known to support T cell migration through induction of cell polarization and lamellipodial formation, the downstream effectors of Mst1 are incompletely defined.

Klebsiella pneumoniae FimK Promotes Virulence in Murine Pneumonia.

Klebsiella pneumoniae, a chief cause of nosocomial pneumonia, is a versatile and commonly multidrug-resistant human pathogen for which further insight into pathogenesis is needed. We show that the pilus regulatory gene fimK promotes the virulence of K. pneumoniae strain TOP52 in murine pneumonia.

Prevalence of nasopharyngeal pneumococcal colonization in children and antimicrobial susceptibility profiles of carriage isolates.

Nasopharyngeal (NP) pneumococcal carriage predisposes children to pneumococcal infections. Defining the proportion of pneumococcal isolates that are antibiotic-resistant enables the appropriate choice of empiric therapies. The antibiogram of NP carriage isolates derived from a pediatric population following the introduction of the 13-valent pneumococcal conjugate vaccine was defined in this study.

L-plastin is essential for alveolar macrophage production and control of pulmonary pneumococcal infection.

We report that mice deficient for the hematopoietic-specific, actin-bundling protein L-plastin (LPL) succumb rapidly to intratracheal pneumococcal infection. The increased susceptibility of LPL(-/-) mice to pulmonary pneumococcal challenge correlated with reduced numbers of alveolar macrophages, consistent with a critical role for this cell type in the immediate response to pneumococcal infection. LPL(-/-) mice demonstrated a very early clearance defect, with an almost 10-fold-higher bacterial burden in the bronchoalveolar lavage fluid 3 h following infection.

Intrinsic T- and B-cell defects impair T-cell-dependent antibody responses in mice lacking the actin-bundling protein L-plastin.

Germinal center development, critical for long-term humoral immunity, requires the trafficking of T and B lymphocytes to defined tissues and locations after antigenic challenge. The molecular mechanisms that support lymphocyte trafficking through the linkage of extracellular chemotactic and adhesive cues to the actin cytoskeleton are not yet fully defined. We have previously identified the actin-bundling protein L-plastin (LPL) as a requisite intermediary in both naive B and T lymphocyte migration and in T-cell activation.

The actin-bundling protein L-plastin is essential for marginal zone B cell development.

B cell development is exquisitely sensitive to location within specialized niches in the bone marrow and spleen. Location within these niches is carefully orchestrated through chemotactic and adhesive cues. In this article, we demonstrate the requirement for the actin-bundling protein L-plastin (LPL) in B cell motility toward the chemokines CXCL12 and CXCL13 and the lipid chemoattractant sphingosine-1-phosphate, which guide normal B cell development.