Age-dependent natural killer cell and interferon γ deficits contribute to severe pertussis in infant mice.

Many respiratory infections are selectively injurious to infants, yet the etiology of age-associated susceptibility is unknown. One such bacterial pathogen is Bordetella pertussis. In adult mice, innate interferon γ (IFN-γ) is produced by natural killer (NK) cells and restricts infection to the respiratory tract.

DNA-Dependent Interferon Induction and Lung Inflammation in Infection.

Pertussis, caused by , is a resurgent respiratory disease but the molecular mechanisms underlying pathogenesis are poorly understood. We recently showed the importance of type I and type III interferon (IFN) induction and signaling for the development of lung inflammation in -infected mouse models. Classically, these IFNs are induced by signaling through a variety of pattern recognition receptors (PRRs) on host cells.

Administering Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer 1-6 Days Compared to More Than 14 Days after the Start of LHRH Agonist Is Associated with Better Clinical Outcomes Due to Androgen Flare.

Docetaxel, when given at the beginning of androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer (MHSPC), results in significantly longer overall survival than ADT alone. We aimed to investigate if the delivery of the first dose of docetaxel during the testosterone flare associated with LHRH initiation results in better clinical outcomes, as testosterone induces mitosis of prostate cancer cells, and docetaxel specifically targets cells in mitosis. We analyzed data from the CHAARTED trial which randomized MHSPC patients to ADT alone or ADT plus docetaxel.

Pertussis Toxin Promotes Pulmonary Hypertension in an Infant Mouse Model of Bordetella pertussis Infection.

Pertussis, caused by Bordetella pertussis, is a reemerging disease that can produce severe disease manifestations in infants, including pulmonary hypertension (PH). B. pertussis-induced PH is a major risk factor for infection-induced death, but the molecular mechanisms promoting PH are unknown and there is no effective treatment.

Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) Contributes to Bordetella pertussis Inflammatory Pathology.

Whooping cough (pertussis) is a severe pulmonary infectious disease caused by the bacteria Bordetella pertussis. Pertussis infects an estimated 24 million people annually, resulting in >150,000 deaths. The NIH placed pertussis on the list of emerging pathogens in 2015.

Attaching-and-Effacing Pathogens Exploit Junction Regulatory Activities of N-WASP and SNX9 to Disrupt the Intestinal Barrier.

Background & Aims: Neural Wiskott-Aldrich Syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton in epithelial tissues and is poised to mediate cytoskeletal-dependent aspects of apical junction complex (AJC) homeostasis. Attaching-and-effacing (AE) pathogens disrupt this homeostasis through translocation of the effector molecule early secreted antigenic target-6 (ESX)-1 secretion-associated protein F (EspF). Although the mechanisms underlying AJC disruption by EspF are unknown, EspF contains putative binding sites for N-WASP and the endocytic regulator sorting nexin 9 (SNX9).

Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways.

In infants, can cause severe disease, manifested as pronounced leukocytosis, pulmonary hypertension, and even death. The exact cause of death remains unknown, and no effective therapies for treating fulminant pertussis exist. In this study, a neonatal mouse model of critical pertussis is characterized, and a central role for pertussis toxin (PT) is described.

The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation.

Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system.

Intracellular disassembly and activity of pertussis toxin require interaction with ATP.

The active subunit (S1) of pertussis toxin (PT), a major virulence factor of Bordetella pertussis, ADP-ribosylates Gi proteins in the mammalian cell cytosol to inhibit GPCR signaling. The intracellular pathway of PT includes endocytosis and retrograde transport to the trans-Golgi network (TGN) and endoplasmic reticulum (ER). Subsequent translocation of S1 to the cytosol is presumably preceded by dissociation from the holotoxin.

Novel therapies for the treatment of pertussis disease.

Whooping cough, or pertussis, incidence has reached levels not seen since the 1950s. Previous studies have shown that antibiotics fail to improve the course of disease unless diagnosed early. Early diagnosis is complicated by the non-diagnostic presentation of disease early in infection.

Epithelial anion transporter pendrin contributes to inflammatory lung pathology in mouse models of Bordetella pertussis infection.

Pertussis disease, characterized by severe and prolonged coughing episodes, can progress to a critical stage with pulmonary inflammation and death in young infants. However, there are currently no effective treatments for pertussis. We previously studied the role of pertussis toxin (PT), an important Bordetella pertussis virulence factor, in lung transcriptional responses to B.

An Escherichia coli effector protein promotes host mutation via depletion of DNA mismatch repair proteins.

Enteropathogenic Escherichia coli (EPEC) is an attaching and effacing (A/E) human pathogen that causes diarrhea during acute infection, and it can also sustain asymptomatic colonization. A/E E. coli depletes host cell DNA mismatch repair (MMR) proteins in colonic cell lines and has been detected in colorectal cancer (CRC) patients.

IL-17A induces CCL28, supporting the chemotaxis of IgE-secreting B cells.

Background: Atopic asthma is an allergic disease typically associated with T(H)2 cytokines. IL-17A is also associated with asthma, through the induction of chemokines. Mucosal CCL28 concentrations correlate with cellular recruitment to inflamed airways and support migration of IgA(+) B cells.