A case of swine influenza A(H1N2)v in England, November 2023.

Under International Health Regulations from 2005, a human infection caused by a novel influenza A virus variant is considered an event that has potential for high public health impact and is immediately notifiable to the World Health Organisation. We here describe the clinical, epidemiological and virological features of a confirmed human case of swine influenza A(H1N2)v in England detected through community respiratory virus surveillance. Swabbing and contact tracing helped refine public health risk assessment, following this unusual and unexpected finding.

Alveolar Macrophage Apoptosis-associated Bacterial Killing Helps Prevent Murine Pneumonia.

Antimicrobial resistance challenges therapy of pneumonia. Enhancing macrophage microbicidal responses would combat this problem but is limited by our understanding of how alveolar macrophages (AMs) kill bacteria. To define the role and mechanism of AM apoptosis-associated bacterial killing in the lung.

Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists.

Rationale: Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms and clinical consequences remain incompletely defined.

Objectives: To examine the effect of COPD on AM phagocytic responses and identify the mechanisms, clinical consequences, and potential for therapeutic manipulation of these defects.

Methods: We isolated AMs and monocyte-derived macrophages (MDMs) from a cohort of patients with COPD and control subjects within the Medical Research Council COPDMAP consortium and measured phagocytosis of bacteria in relation to opsonic conditions and clinical features.

HIV gp120 in the Lungs of Antiretroviral Therapy-treated Individuals Impairs Alveolar Macrophage Responses to Pneumococci.

Rationale: People living with HIV are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains undefined.

Objectives: To determine if apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed.

Bacterial size matters: Multiple mechanisms controlling septum cleavage and diplococcus formation are critical for the virulence of the opportunistic pathogen Enterococcus faecalis.

Enterococcus faecalis is an opportunistic pathogen frequently isolated in clinical settings. This organism is intrinsically resistant to several clinically relevant antibiotics and can transfer resistance to other pathogens. Although E.

Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages.

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria.

Objectives: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated.

Methods: AMs were obtained from bronchoalveolar lavage from healthy donors or patients with COPD and challenged with opsonized serotype 14 Streptococcus pneumoniae.

Differential Effects of p38, MAPK, PI3K or Rho Kinase Inhibitors on Bacterial Phagocytosis and Efferocytosis by Macrophages in COPD.

Pulmonary inflammation and bacterial colonization are central to the pathogenesis of chronic obstructive pulmonary disease (COPD). Defects in macrophage phagocytosis of both bacteria and apoptotic cells contribute to the COPD phenotype. Small molecule inhibitors with anti-inflammatory activity against p38 mitogen activated protein kinases (MAPKs), phosphatidyl-inositol-3 kinase (PI3K) and Rho kinase (ROCK) are being investigated as novel therapeutics in COPD.

The anti-inflammatory effects of PGE on human lung macrophages are mediated by the EP receptor.

Background And Purpose: PGE inhibits cytokine generation from human lung macrophages. However, the EP receptor that mediates this beneficial anti-inflammatory effect of PGE has not been defined. The aim of this study was to identify the EP receptor by which PGE inhibits cytokine generation from human lung macrophages.

Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages.

Macrophages are critical effectors of the early innate response to bacteria in tissues. Phagocytosis and killing of bacteria are interrelated functions essential for bacterial clearance but the rate-limiting step when macrophages are challenged with large numbers of the major medical pathogen Staphylococcus aureus is unknown. We show that macrophages have a finite capacity for intracellular killing and fail to match sustained phagocytosis with sustained microbial killing when exposed to large inocula of S.

Pneumolysin activates macrophage lysosomal membrane permeabilization and executes apoptosis by distinct mechanisms without membrane pore formation.

Intracellular killing of Streptococcus pneumoniae is complemented by induction of macrophage apoptosis. Here, we show that the toxin pneumolysin (PLY) contributes both to lysosomal/phagolysosomal membrane permeabilization (LMP), an upstream event programing susceptibility to apoptosis, and to apoptosis execution via a mitochondrial pathway, through distinct mechanisms. PLY is necessary but not sufficient for the maximal induction of LMP and apoptosis.

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci.

Proteomic evaluation and validation of cathepsin D regulated proteins in macrophages exposed to Streptococcus pneumoniae.

Macrophages are central effectors of innate immune responses to bacteria. We have investigated how activation of the abundant macrophage lysosomal protease, cathepsin D, regulates the macrophage proteome during killing of Streptococcus pneumoniae. Using the cathepsin D inhibitor pepstatin A, we demonstrate that cathepsin D differentially regulates multiple targets out of 679 proteins identified and quantified by eight-plex isobaric tag for relative and absolute quantitation.

A cardinal role for cathepsin d in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci.

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis.

Distinct cell death programs in monocytes regulate innate responses following challenge with common causes of invasive bacterial disease.

Peripheral blood monocytes represent the rapid response component of mononuclear phagocyte host defense, generating vigorous but finite antibacterial responses. We investigated the fate of highly purified primary human monocytes following phagocytosis of different bacteria. Exposure to high bacterial loads resulted in rapid loss of cell viability and decreased functional competence.

Subversion of a lysosomal pathway regulating neutrophil apoptosis by a major bacterial toxin, pyocyanin.

Neutrophils undergo rapid constitutive apoptosis that is accelerated following bacterial ingestion as part of effective immunity, but is also accelerated by bacterial exotoxins as a mechanism of immune evasion. The paradigm of pathogen-driven neutrophil apoptosis is exemplified by the Pseudomonas aeruginosa toxic metabolite, pyocyanin. We previously showed pyocyanin dramatically accelerates neutrophil apoptosis both in vitro and in vivo, impairs host defenses, and favors bacterial persistence.