Leukocyte kinetics and bacterial clearance during pneumonia and contributions of ICAM-1.

is a leading cause of community-acquired pneumonia. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that is highly expressed on the pulmonary capillary endothelium, alveolar epithelium, and other cell types within the lung. ICAM-1 plays important roles in leukocyte adhesion, migration, and motility.

Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli.

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single-dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice.

Neutrophils sing "IL[-10] be seeing you" in the lungs during pneumonia.

Mechanisms of regulating the beneficial and harmful capabilities of neutrophils include IL-10/IL-10RA signaling in neutrophils that limits clearance of Streptococcus pneumoniae and accumulation of neutrophils in pneumonic lung tissue.

TBK1 Is Required for Host Defense Functions Distinct from Type I IFN Expression and Myeloid Cell Recruitment in Murine Pneumonia.

Bacterial pneumonia induces the rapid recruitment and activation of neutrophils and macrophages into the lung, and these cells contribute to bacterial clearance and other defense functions. TBK1 (TANK-binding kinase 1) performs many functions, including activation of the type I IFN pathway and regulation of autophagy and mitophagy, but its contribution to antibacterial defenses in the lung is unclear. We previously showed that lung neutrophils upregulate mRNAs for TBK1 and its accessory proteins during pneumonia, despite low or absent expression of type I IFN in these cells.

Neutrophil DREAM come true: The not-so-impossible quest for mechanisms of neutrophil function and heterogeneity.

Neutrophil functions and responses are heterogeneous, and the nature and categorization of this heterogeneity is achieving considerable interest. Work by Li et al. in this issue of JEM (2021.

Dynamic changes in lung responses after single and repeated exposures to cigarette smoke in mice.

Cigarette smoke is well recognized to cause injury to the airways and the alveolar walls over time. This injury usually requires many years of exposure, suggesting that the lungs may rapidly develop responses that initially protect it from this repetitive injury. Our studies tested the hypotheses that smoke induces an inflammatory response and changes in mRNA profiles that are dependent on sex and the health status of the lung, and that the response of the lungs to smoke differs after 1 day compared to 5 days of exposure.

Transcriptional analysis of Foxp3+ Tregs and functions of two identified molecules during resolution of ALI.

Recovery from acute lung injury (ALI) is an active process. Foxp3+ Tregs contribute to recovery from ALI through modulating immune responses and enhancing alveolar epithelial proliferation and tissue repair. The current study investigates Treg transcriptional profiles during resolution of ALI in mice.

Predicted effects of observed changes in the mRNA and microRNA transcriptome of lung neutrophils during S. pneumoniae pneumonia in mice.

The complex role of neutrophils in modulating the inflammatory response is increasingly appreciated. Our studies profiled the expression of mRNAs and microRNAs (miRs) in lung neutrophils in mice during S. pneumoniae pneumonia and performed in depth in silico analyses.

Biomarkers of exposure to new and emerging tobacco delivery products.

Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products.

Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.

Nrf2 regulates the transcriptional response to oxidative stress. These studies tested the role of Nrf2 during Streptococcus pneumoniae pneumonia and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils. Nrf2 null and wild type (WT) mice were studied at 6 and 24 h after instillation of S.

Mechanisms of interferon-γ production by neutrophils and its function during Streptococcus pneumoniae pneumonia.

Bacterial pneumonia is a common public health problem associated with significant mortality, morbidity, and cost. Neutrophils are usually the earliest leukocytes to respond to bacteria in the lungs. Neutrophils rapidly sequester in the pulmonary microvasculature and migrate into the lung parenchyma and alveolar spaces, where they perform numerous effector functions for host defense.

Interferon-γ production by neutrophils during bacterial pneumonia in mice.

Rationale: Neutrophils are usually the first circulating leukocytes to respond during bacterial pneumonia. Their expression of oxidants, proteases, and other mediators present in granules is well documented, but their ability to produce mediators through transcription and translation after migration to an inflammatory site has been appreciated only more recently. Interferon (IFN)-γ is a cytokine with many functions important in host defense and immunity.

The role of CD18 in the production and release of neutrophils from the bone marrow.

Neutrophil numbers must be tightly controlled to maintain host protection and prevent neutrophil-mediated tissue injury. CD18 deficiency leads to neutrophilia and myeloid hyperplasia in the bone marrow (BM). These studies examined the function of CD18 in regulating neutrophil production and determined whether the defects in neutrophil production that are observed in CD18 deficiency persist in the presence of wild-type (WT) leukocytes that confer host protection.

The role of Rac2 in regulating neutrophil production in the bone marrow and circulating neutrophil counts.

Circulating neutrophils are persistently higher in mice deficient in the small GTPase Rac2 than in wild-type (WT) mice. Therefore, we examined the mechanisms through which the small GTPase Rac2 regulates neutrophil production and release. Lethally irradiated WT mice reconstituted with a 50:50 mixture of WT and Rac2(-/-) fetal liver cells were protected from neutrophilia, suggesting that neutrophilia is primarily because of extrinsic defects that can be corrected by WT leukocytes.

Identification of a polymorphic Plasmodium vivax microsatellite marker.

Microsatellite markers derived from simple sequence repeats have been useful in studying a number of human pathogens, including the human malaria parasite Plasmodium falciparum. Genetic markers for P. vivax would likewise help elucidate the genetics and population characteristics of this other important human malaria parasite.