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Journal of Leukocyte Biology

Angharad Grace Davis, Ursula Karin Rohlwink, Alizé Proust, Anthony A Figaji, Robert J Wilkinson
Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury...
January 15, 2019: Journal of Leukocyte Biology
Pierre Cunin, Peter A Nigrovic
Platelets play well-recognized roles in inflammation, but their cell of origin-the megakaryocyte-is not typically considered an immune lineage. Megakaryocytes are large polyploid cells most commonly identified in bone marrow. Egress via sinusoids enables migration to the pulmonary capillary bed, where elaboration of platelets can continue. Beyond receptors involved in hemostasis and thrombosis, megakaryocytes express receptors that confer immune sensing capacity, including TLRs and Fc-γ receptors. They control the proliferation of hematopoietic cells, facilitate neutrophil egress from marrow, possess the capacity to cross-present antigen, and can promote systemic inflammation through microparticles rich in IL-1...
January 15, 2019: Journal of Leukocyte Biology
Elisa Zaghi, Michela Calvi, Emanuela Marcenaro, Domenico Mavilio, Clara Di Vito
Natural Killer (NK) cells are innate immune cells with a primary role in the immune surveillance against non-self-cells. NK cell recognition of "self" relies on the surface expression on autologous cells of MHC class I (MHC-I) molecules. Either the absence or the down-modulation of MHC-I on target cells "license" NK cells to kill threatening tumor-transformed or virally infected cells. This phenomenon is controlled by a limited repertoire of activating and inhibitory NK receptors (aNKRs and iNKRs) that tunes NK cell activation and effector functions...
January 15, 2019: Journal of Leukocyte Biology
Monowar Aziz, Max Brenner, Ping Wang
Cold-inducible RNA-binding protein (CIRP) was discovered 2 decades ago while studying the mechanism of cold stress adaptation in mammals. Since then, the role of intracellular CIRP (iCIRP) as a stress-response protein has been extensively studied. Recently, extracellular CIRP (eCIRP) was discovered to also have an important role, acting as a damage-associated molecular pattern, raising critical implications for the pathobiology of inflammatory diseases. During hemorrhagic shock and sepsis, inflammation triggers the translocation of CIRP from the nucleus to the cytosol and its release to the extracellular space...
January 15, 2019: Journal of Leukocyte Biology
Liliana Torres-López, Paola Maycotte, Andrómeda Liñán-Rico, Liliana Liñán-Rico, Luis Donis-Maturano, Iván Delgado-Enciso, Carmen Meza-Robles, Clemente Vásquez-Jiménez, Arturo Hernández-Cruz, Oxana Dobrovinskaya
Estrogens demonstrate biological activity in numerous organ systems, including the immune system, and exert their effects through estrogen receptors (ER) of two types: intracellular ERα and ERβ that activate transcriptional factors and membrane G protein-coupled ER GPER. The latter is capable to mediate fast activation of cytosolic signaling pathways, influencing transcriptional events in response to estrogens. Tamoxifen (TAM), widely used in chemotherapy of ERα-positive breast cancer, is considered as an ERα antagonist and GPER agonist...
January 15, 2019: Journal of Leukocyte Biology
Hemant Joshi, Sharon Celeste Morley
Many intracellular signals, such as host danger-associated molecules and bacterial toxins during infection, elicit inflammasome activation. However, the mechanical environment in tissues may also influence the sensitivity of various inflammasomes to activation. The cellular mechanical environment is determined by the extracellular tissue stiffness, or its inverse, tissue compliance. Tissue stiffness is sensed by the intracellular cytoskeleton through a process termed mechanotransduction. Thus, extracellular compliance and the intracellular cytoskeleton may regulate the sensitivity of inflammasome activation...
January 15, 2019: Journal of Leukocyte Biology
Xuewei Zhu, Allison Meyers, David Long, Brian Ingram, Tiefu Liu, Barbara K Yoza, Vidula Vachharajani, Charles E McCall
Metabolism directs the severe acute inflammatory reaction of monocytes to guard homeostasis. This occurs by sequentially activating anabolic immune effector mechanisms, switching to immune deactivation mechanisms and then restoring immunometabolic homeostasis. Nuclear sirtuin 1 and mitochondrial pyruvate dehydrogenase kinase metabolically drive this dynamic and are druggable targets that promote immunometabolic resolution in septic mice and increase survival. We used unbiased metabolomics and a validated monocyte culture model of activation, deactivation, and partial resolution of acute inflammation to sequentially track metabolic rewiring...
January 11, 2019: Journal of Leukocyte Biology
Jianfeng Xie, Rebecca L Crepeau, Ching-Wen Chen, Wenxiao Zhang, Shunsuke Otani, Craig M Coopersmith, Mandy L Ford
Epstein-Barr virus (EBV) reactivation commonly occurs following sepsis, but the mechanisms underlying this are unknown. We utilized a murine EBV homolog (gHV) and the cecal ligation and puncture model of polymicrobial sepsis to study the impact of sepsis on gHV reactivation and CD8+ T cell immune surveillance following a septic insult. We observed a significant increase in the frequency of gHV-infected germinal center B cells on day 7 following sepsis. This increase in viral load was associated with a concomitant significant decrease in the frequencies of gHV-specific CD8+ T cells, as measured by class I MHC tetramers corresponding to the immunodominant viral epitopes...
January 9, 2019: Journal of Leukocyte Biology
Naeem K Patil, Julia K Bohannon, Edward R Sherwood
No abstract text is available yet for this article.
January 7, 2019: Journal of Leukocyte Biology
Sakshum Chadha, Liqing Wang, Wayne W Hancock, Ulf H Beier
Sirtuin-1 (Sirt1), a member of the NAD-dependent sirtuin family of histone/protein deacetylases (HDAC), is an important target for immunotherapy due to its role in deacetylating the transcription factors Foxp3 and thymic retinoid acid receptor related orphan receptor gamma (RORγt). Sirt1 inhibition can increase Foxp3 acetylation and promote the production and functions of Foxp3+ T-regulatory (Treg) cells, whereas the acetylation of RORγt decreases its transcriptional activity DNA binding and decreases the differentiation of proinflammatory Th17 cells...
January 3, 2019: Journal of Leukocyte Biology
David Verhoeven
Although children growing from birth into young adulthood undergo rapid physiological maturation, their immune systems are also undergoing significant changes that may affect how they respond to microbes and especially respiratory pathogens. A key component of control over microbes is the innate immune system that sustains pathogen suppression/elimination until the adaptive immune system can instigate clearance. Here, this review will summarize key characteristics of the developing innate immune system of neonates, infants, and toddlers...
January 3, 2019: Journal of Leukocyte Biology
Monica Yabal, Dale J Calleja, Daniel S Simpson, Kate E Lawlor
Inflammasomes are multimeric protein complexes that induce the cleavage and release of bioactive IL-1β and cause a lytic form of cell death, termed pyroptosis. Due to its diverse triggers, ranging from infectious pathogens and host danger molecules to environmental irritants, the NOD-like receptor protein 3 (NLRP3) inflammasome remains the most widely studied inflammasome to date. Despite intense scrutiny, a universal mechanism for its activation remains elusive, although, recent research has focused on mitochondrial dysfunction or potassium (K+ ) efflux as key events...
December 27, 2018: Journal of Leukocyte Biology
Hatem Masmoudi, Olfa Abida, Abderrahmen Masmoudi, Hamida Turki
Pemphigus foliaceus (PF) is an autoimmune blistering skin disease characterized by the presence of bullous skin lesions, the absence of mucous tissue involvement, and the production of auto-antibodies directed against a keratinocyte transmembrane protein localized in the desmosome and member of the cadherines, desmoglein 1. These pathogenic auto-antibodies are responsible for the intra-epidermal formation of blisters through the loss of keratinocyte adhesion, the so-called acantholysis process. The endemic form of PF observed in the south of Tunisia is characterized by a significantly higher incidence rate compared to the sporadic form in northern countries, occurrence mainly in young women and the absence of cases during childhood...
December 21, 2018: Journal of Leukocyte Biology
Sonwabile Dzanibe, Heather B Jaspan, Michael Z Zulu, Agano Kiravu, Clive M Gray
At least one-third of infants born in sub-Saharan Africa have been exposed to the effects of maternal HIV infection and antiretroviral treatment. Intrauterine HIV exposure is associated with increased rates of morbidity and mortality in children. Although the mechanisms responsible for poor infant health with HIV-1 exposure are likely to be multifactorial, we posit that the maternal environment during gestation and in the perinatal period results in altered infant immunity and is possibly the strongest contributing factor responsible for the disproportionally high infectious events among HIV-exposed infants who remain HIV uninfected...
December 21, 2018: Journal of Leukocyte Biology
Selena Y Cen, Joshua M Moreau, Caren Furlonger, Alexandra Berger, Christopher J Paige
B cell development is regulated by stromal cells (SCs) that form a supportive microenvironment. These SCs along with other cell types produce cytokines, chemokines, and adhesion molecules that guide B cell commitment and differentiation. BM, spleen (Sp), and the gut lamina propria (LP) constitute distinctive anatomical compartments that support B cell differentiation. In order to characterize and compare the signals necessary to generate IgA+ B cells, we developed an in vitro system to co-culture gut LP, BM, or Sp-derived SCs with B lineage cells...
December 21, 2018: Journal of Leukocyte Biology
Miranda J Crouch, Rasagna Kosaraju, William Guesdon, Michael Armstrong, Nichole Reisdorph, Raghav Jain, Jenifer Fenton, Saame Raza Shaikh
Obesity dysregulates B cell populations, which contributes toward poor immunological outcomes. We previously reported that differing B cell subsets are lowered in the bone marrow of obese male mice. Here, we focused on how lipid metabolites synthesized from docosahexaenoic acid (DHA) known as specialized pro-resolving lipid mediators (SPMs) influence specific B cell populations in obese male mice. Metabololipidomics revealed that splenic SPM precursors 14-hydroxydocosahexaenoic acid (14-HDHA), 17-hydroxydocosahexaenoic acid (17-HDHA), and downstream protectin DX (PDX) were decreased in obese male C57BL/6J mice...
December 21, 2018: Journal of Leukocyte Biology
Le-Xun Wang, Sheng-Xi Zhang, Hui-Juan Wu, Xiang-Lu Rong, Jiao Guo
Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages. Macrophages commonly exist in two distinct subsets: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2b, a subtype of M2 macrophages, has attracted increasing attention over the past decade due to its strong immune-regulated and anti-inflammatory effects. A wide variety of stimuli and multiple factors modulate M2b macrophage polarization in vitro and in vivo...
December 21, 2018: Journal of Leukocyte Biology
Elena Pontarini, Davide Lucchesi, Liliane Fossati-Jimack, Rachel Coleby, Paolo Tentorio, Cristina Croia, Michele Bombardieri, Domenico Mavilio
Salivary glands (SGs) represent a permissive site for several sialotropic viruses whose persistence is linked to the development of autoimmunity. Natural Killer (NK) cells play a key role in viral clearance but their involvement in viral infection control and in tertiary lymphoid structures (TLS) development within SGs is unknown. By using an inducible model of TLS in the SGs of wild-type C57BL/6 mice, induced by the local delivery of a replication-defective adenovirus (AdV), we demonstrated that circulating NK cells are rapidly recruited to SGs and highly enrich the early inflammatory infiltrate prior to TLS development...
December 21, 2018: Journal of Leukocyte Biology
Jason P Mooney, Lauren J Galloway, Eleanor M Riley
Invasive bacterial disease is well described in immunocompromised hosts, including those with malaria infection. One bacterial infection frequently observed in children with Plasmodium falciparum infection is nontyphoidal salmonella (NTS) infection, in which a typically intestinal infection becomes systemic with serious, often fatal, consequences. In this review, we consider the role of malaria-induced immunoregulatory responses in tipping the balance from tissue homeostasis during malaria infection to risk of invasive NTS...
December 20, 2018: Journal of Leukocyte Biology
Lena Björkman, Karin Christenson, Lisa Davidsson, Jonas Mårtensson, Firoozeh Amirbeagi, Amanda Welin, Huamei Forsman, Anna Karlsson, Claes Dahlgren, Johan Bylund
Recruitment of neutrophils from blood to tissues is a cardinal event in inflammation during which neutrophils switch from a resting, naive state to a preactivated, primed phenotype; the priming process is characterized by alterations in the composition of cell surface adhesins, for example, shedding of l-selectin and mobilization of granule-stored integrins to the cell surface. Ligation of chemotactic receptors and interactions with the endothelial lining are established triggers of neutrophil priming and in line with this, in vivo transmigrated neutrophils obtained from tissues are typically highly primed...
December 20, 2018: Journal of Leukocyte Biology
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