Tim4- and MerTK-mediated engulfment of apoptotic cells by mouse resident peritoneal macrophages.
AuthorsNishi C, Toda S, Segawa K, Nagata S,
Journal
PubMed ID24515440
'Apoptotic cells are swiftly engulfed by macrophages to prevent the release of noxious materials from dying cells. Apoptotic cells expose phosphatidylserine (PtdSer) on their surface, and macrophages engulf them by recognizing PtdSer using specific receptors and opsonins. Here, we found that mouse resident peritoneal macrophages expressing Tim4 and MerTK are ... More
The effect of endosomal escape peptides on in vitro gene delivery of polyethylene glycol-based vehicles.
AuthorsMoore NM, Sheppard CL, Barbour TR, Sakiyama-Elbert SE,
JournalJ Gene Med
PubMed ID18642401
'BACKGROUND: With recent progress in gene therapy clinical trials, there is an even greater demand to advance the development of nonviral gene delivery vehicles. We have previously developed poly(ethylene glycol) (PEG)-based vehicles with transfection efficiency similar to polyethyleneimine and low cytotoxicity. It was hypothesized that conjugating endosomal escape peptides (EEPs) ... More
Initial cytoplasmic and phagosomal consequences of human neutrophil exposure to Staphylococcus epidermidis.
AuthorsBernardo J, Long HJ, Simons ER,
JournalCytometry A
PubMed ID19937952
'Microorganisms are recognized by specific phagocyte surface receptors. Liganded receptors then signal a series of events leading to phagocytosis and destruction of the organism by oxidative, lytic, and associated processes. Some organisms, such as Mycobacterium tuberculosis (Mtb), Cryptococcus neoformans (Cf), and others, evade such destruction, surviving and sometimes multiplying within ... More
Zebrafish as a novel vertebrate model to dissect enterococcal pathogenesis.
'Enterococcus faecalis is an opportunistic pathogen responsible for a wide range of life-threatening nosocomial infections, such as septicemia, peritonitis, and endocarditis. E. faecalis infections are associated with a high mortality and substantial health care costs and cause therapeutic problems due to the intrinsic resistance of this bacterium to antibiotics. Several ... More
Engulfing Astrocytes Protect Neurons from Contact-Induced Apoptosis following Injury.
AuthorsLööv C, Hillered L, Ebendal T, Erlandsson A,
JournalPLoS One
PubMed ID22461890
'Clearing of dead cells is a fundamental process to limit tissue damage following brain injury. Engulfment has classically been believed to be performed by professional phagocytes, but recent data show that non-professional phagocytes are highly involved in the removal of cell corpses in various situations. The role of astrocytes in ... More
Phagocytosis of apoptotic cells by neutrophil granulocytes: diminished proinflammatory neutrophil functions in the presence of apoptotic cells.
AuthorsEsmann L, Idel C, Sarkar A, Hellberg L, Behnen M, Möller S, van Zandbergen G, Klinger M, Köhl J, Bussmeyer U, Solbach W, Laskay T,
JournalJ Immunol
PubMed ID19949068
'Neutrophil granulocytes are rapidly recruited from the bloodstream to the site of acute inflammation where they die in large numbers. Because release of toxic substances from dead neutrophils can propagate the inflammatory response leading to tissue destruction, clearance of dying inflammatory neutrophils has a critical function in the resolution of ... More
Innate immunity against Granulibacter bethesdensis, an emerging gram-negative bacterial pathogen.
AuthorsZarember KA, Marshall-Batty KR, Cruz AR, Chu J, Fenster ME, Shoffner AR, Rogge LS, Whitney AR, Czapiga M, Song HH, Shaw PA, Nagashima K, Malech HL, DeLeo FR, Holland SM, Gallin JI, Greenberg DE,
JournalInfect Immun
PubMed ID22184421
'Acetic acid bacteria were previously considered nonpathogenic in humans. However, over the past decade, five genera of Acetobacteraceae have been isolated from patients with inborn or iatrogenic immunodeficiencies. Here, we describe the first studies of the interactions of the human innate immune system with a member of this bacterial family, ... More
Editing antigen presentation: antigen transfer between human B lymphocytes and macrophages mediated by class A scavenger receptors.
AuthorsHarvey BP, Quan TE, Rudenga BJ, Roman RM, Craft J, Mamula MJ,
JournalJ Immunol
PubMed ID18768860
'B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated by B cell APCs. This finding led us to identify a process in mice whereby Ag-specific B cells transfer Ag to other APCs. In ... More
A new flow-cytometry-based opsonophagocytosis assay for the rapid measurement of functional antibody levels against Group B Streptococcus.
AuthorsFabbrini M, Sammicheli C, Margarit I, Maione D, Grandi G, Giuliani MM, Mori E, Nuti S,
JournalJ Immunol Methods
PubMed ID22309986
'Opsonophagocytosis is the primary mechanism for the clearance of Group B Streptococcus (GBS) by the host, and levels of opsonic antibodies may correlate with protection in preclinical models. A killing-based opsonophagocytosis assay (OPA), can be used to determine the functional activity of vaccine-induced GBS-specific antibodies. The assay, which measures the ... More
Fluorescent indicators for intracellular pH.
AuthorsHan J, Burgess K,
JournalChem Rev
PubMed ID19831417
This review is about intracellular pH sensors, includingsmall fluorescent organic molecules, nanoparticles, andfluorescent proteins, e.g., GFP. It focuses on their preparations, photophysical properties, and advantages/disadvantagesfor intracellular pH measurements. The discussion is limitedto fluorescent indicators that have been applied to measureintracellular pH values since 1980. ... More
SIRPa polymorphisms, but not the prion protein, control phagocytosis of apoptotic cells.
AuthorsNuvolone M, Kana V, Hutter G, Sakata D, Mortin-Toth SM, Russo G, Danska JS, Aguzzi A,
Journal
PubMed ID24145514
Prnp(-/-) mice lack the prion protein PrP(C) and are resistant to prion infections, but variable phenotypes have been reported in Prnp(-/-) mice and the physiological function of PrP(C) remains poorly understood. Here we examined a cell-autonomous phenotype, inhibition of macrophage phagocytosis of apoptotic cells, previously reported in Prnp(-/-) mice. Using ... More
Persistence of the bacterial pathogen Granulibacter bethesdensis in chronic granulomatous disease monocytes and macrophages lacking a functional NADPH oxidase.
AuthorsChu J, Song HH, Zarember KA, Mills TA, Gallin JI,
Journal
PubMed ID23956436
Granulibacter bethesdensis is a Gram-negative pathogen in patients with chronic granulomatous disease (CGD), a deficiency in the phagocyte NADPH oxidase. Repeated isolation of genetically identical strains from the same patient over years, and prolonged waxing and waning seropositivity in some subjects, raises the possibility of long-term persistence. G. bethesdensis resists ... More
Connexin43 is dispensable for phagocytosis.
AuthorsGlass AM, Wolf BJ, Schneider KM, Princiotta MF, Taffet SM,
JournalJ Immunol
PubMed ID23554311
Macrophages that lack connexin43 (Cx43), a gap junction protein, have been reported to exhibit dramatic deficiencies in phagocytosis. In this study, we revisit these findings using well-characterized macrophage populations. Cx43 knockout (Cx43(-/-)) mice die soon after birth, making the harvest of macrophages from adult Cx43(-/-) mice problematic. To overcome this ... More
Urease activity represents an alternative pathway for Mycobacterium tuberculosis nitrogen metabolism.
AuthorsLin W, Mathys V, Ang EL, Koh VH, Martínez Gómez JM, Ang ML, Zainul Rahim SZ, Tan MP, Pethe K, Alonso S,
JournalInfect Immun
PubMed ID22645285
Urease represents a critical virulence factor for some bacterial species through its alkalizing effect, which helps neutralize the acidic microenvironment of the pathogen. In addition, urease serves as a nitrogen source provider for bacterial growth. Pathogenic mycobacteria express a functional urease, but its role during infection has yet to be ... More
Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes.
Dendritic cells (DCs) are the most potent APCs. Whereas immature DCs down-regulate T-cell responses to induce/maintain immunologic tolerance, mature DCs promote immunity. To amplify their functions, DCs communicate with neighboring DCs through soluble mediators, cell-to-cell contact, and vesicle exchange. Transfer of nanovesicles (< 100 nm) derived from the endocytic pathway ... More
A novel method to determine the engulfment of apoptotic cells by macrophages using pHrodo succinimidyl ester.
AuthorsMiksa M, Komura H, Wu R, Shah KG, Wang P,
JournalJ Immunol Methods
PubMed ID19135446
Apoptotic cell phagocytosis has recently raised considerable interest, particularly due to its intricate molecular mechanisms and negative immunologic impact of incompetent clearance of apoptotic cells. There is a need for simple and reliable methods to clearly determine the internalization of apoptotic cells. Labeling with pHrodo succinimidyl ester (SE), a pH-sensitive ... More
Transport to late endosomes is required for efficient reovirus infection.
AuthorsMainou BA, Dermody TS,
JournalJ Virol
PubMed ID22674975
Rab GTPases play an essential role in vesicular transport by coordinating the movement of various types of cargo from one cellular compartment to another. Individual Rab GTPases are distributed to specific organelles and thus serve as markers for discrete types of endocytic vesicles. Mammalian reovirus binds to cell surface glycans ... More
High sensitivity detection of cancer in vivo using a dual-controlled activation fluorescent imaging probe based on H-dimer formation and pH activation.
AuthorsOgawa M, Kosaka N, Regino CA, Mitsunaga M, Choyke PL, Kobayashi H,
JournalMol Biosyst
PubMed ID20567775
The key to improving the sensitivity of in vivo molecular imaging is to increase the target-to-background signal ratio (TBR). Optical imaging has a distinct advantage over other molecular imaging methods in that the fluorescent signal can be activated at the target thus reducing background signal. Previously, we found that H-dimer ... More
Two-step engulfment of apoptotic cells.
AuthorsToda S, Hanayama R, Nagata S,
JournalMol Cell Biol
PubMed ID22037761
Apoptotic cells expose phosphatidylserine on their surface as an "eat me" signal, and macrophages respond by engulfing them. Although several molecules that specifically bind phosphatidylserine have been identified, the molecular mechanism that triggers engulfment remains elusive. Here, using a mouse pro-B cell line, Ba/F3, that grows in suspension, we reconstituted ... More
Antibody-mediated clearance of tau in primary mouse microglial cultures requires Fc?-receptor binding and functional lysosomes.
AuthorsAndersson CR, Falsig J, Stavenhagen JB, Christensen S, Kartberg F, Rosenqvist N, Finsen B, Pedersen JT
JournalSci Rep
PubMed ID30874605
'Neurodegenerative diseases such as Alzheimer''s disease are characterized by the progressive spreading and accumulation of hyper-phosphorylated tau protein in the brain. Anti-tau antibodies have been shown to reduce tau pathology in in vivo models and antibody-mediated clearance of tau exerted by microglia has been proposed as a contributing factor. By ... More
CNS-resident classical DCs play a critical role in CNS autoimmune disease.
AuthorsGiles DA, Duncker PC, Wilkinson NM, Washnock-Schmid JM, Segal BM
JournalJ Clin Invest
PubMed ID30226829
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS), induced by the adoptive transfer of myelin-reactive CD4+ T cells into naive syngeneic mice. It is widely used as a rodent model of multiple sclerosis (MS). The development of EAE lesions is initiated when transferred ... More
Neutrophils enhance early Trypanosoma brucei infection onset.
AuthorsCaljon G, Mabille D, Stijlemans B, De Trez C, Mazzone M, Tacchini-Cottier F, Malissen M, A Van Ginderachter J, Magez S, De Baetselier P, Van Den Abbeele J
JournalSci Rep
PubMed ID30046157
In this study, Trypanosoma brucei was naturally transmitted to mice through the bites of infected Glossina morsitans tsetse flies. Neutrophils were recruited rapidly to the bite site, whereas monocytes were attracted more gradually. Expression of inflammatory cytokines (il1b, il6), il10 and neutrophil chemokines (cxcl1, cxcl5) was transiently up-regulated at the ... More
Epigenetic regulation of brain region-specific microglia clearance activity.
AuthorsAyata P, Badimon A, Strasburger HJ, Duff MK, Montgomery SE, Loh YE, Ebert A, Pimenova AA, Ramirez BR, Chan AT, Sullivan JM, Purushothaman I, Scarpa JR, Goate AM, Busslinger M, Shen L, Losic B, Schaefer A
JournalNat Neurosci
PubMed ID30038282
The rapid elimination of dying neurons and nonfunctional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depends on the rate of neuronal attrition. Cerebellar, but not striatal ... More
C3a is required for ILC2 function in allergic airway inflammation.
AuthorsGour N, Smole U, Yong HM, Lewkowich IP, Yao N, Singh A, Gabrielson E, Wills-Karp M, Lajoie S
JournalMucosal Immunol
PubMed ID30104625
Aberrant type 2 responses underlie the pathologies in allergic diseases like asthma, yet, our understanding of the mechanisms that drive them remains limited. Recent evidence suggests that dysregulated innate immune factors can perpetuate asthma pathogenesis. In susceptible individuals, allergen exposure triggers the activation of complement, a major arm of innate ... More
CLIC4/Arf6 Pathway.
AuthorsAbdul-Salam VB, Russomanno G, Chien-Nien C, Mahomed AS, Yates LA, Wilkins MR, Zhao L, Gierula M, Dubois O, Schaeper U, Endruschat J, Wojciak-Stothard B
JournalCirc Res
PubMed ID30582444
Increased expression of CLIC4 (chloride intracellular channel 4) is a feature of endothelial dysfunction in pulmonary arterial hypertension, but its role in disease pathology is not fully understood. ... More