Metabolic reprogramming of the myeloid lineage by Schistosoma mansoni infection persists independently of antigen exposure.
AuthorsCortes-Selva D, Gibbs L, Maschek JA, Nascimento M, Van Ry T, Cox JE, Amiel E, Fairfax KC
JournalPLoS Pathog
PubMed ID33417618
'Macrophages have a defined role in the pathogenesis of metabolic disease and cholesterol metabolism where alternative activation of macrophages is thought to be beneficial to both glucose and cholesterol metabolism during high fat diet induced disease. It is well established that helminth infection protects from metabolic disease, but the mechanisms ... More
Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation.
AuthorsBuerger C, Shirsath N, Lang V, Berard A, Diehl S, Kaufmann R, Boehncke WH, Wolf P
JournalPLoS One
PubMed ID28700632
'Psoriasis is a frequent and often severe inflammatory skin disease, characterized by altered epidermal homeostasis. Since we found previously that Akt/mTOR signaling is hyperactivated in psoriatic skin, we aimed at elucidating the role of aberrant mTORC1 signaling in this disease. We found that under healthy conditions mTOR signaling was shut ... More
T-cell-expressed proprotein convertase FURIN inhibits DMBA/TPA-induced skin cancer development.
AuthorsVähätupa M, Aittomäki S, Martinez Cordova Z, May U, Prince S, Uusitalo-Järvinen H, Järvinen TA, Pesu M
JournalOncoimmunology
PubMed ID28123881
'Proprotein convertases (PCSK) have a critical role in the body homeostasis as enzymes responsible for processing precursor proteins into their mature forms. FURIN, the first characterized member of the mammalian PCSK family, is overexpressed in multiple malignancies and the inhibition of its activity has been considered potential cancer treatment. FURIN ... More
Long-Lived CD4+IFN-?+ T Cells rather than Short-Lived CD4+IFN-?+IL-10+ T Cells Initiate Rapid IL-10 Production To Suppress Anamnestic T Cell Responses during Secondary Malaria Infection.
AuthorsVillegas-Mendez A, Inkson CA, Shaw TN, Strangward P, Couper KN
JournalJ Immunol
PubMed ID27630165
CD4
Induction of VEGFA and Snail-1 by meningitic Escherichia coli mediates disruption of the blood-brain barrier.
AuthorsYang R, Liu W, Miao L, Yang X, Fu J, Dou B, Cai A, Zong X, Tan C, Chen H, Wang X
JournalOncotarget
PubMed ID27588479
Escherichia coli is the most common Gram-negative bacterium that possesses the ability to cause neonatal meningitis, which develops as circulating bacteria penetrate the blood-brain barrier (BBB). However, whether meningitic E. coli could induce disruption of the BBB and the underlying mechanisms are poorly understood. Our current work highlight for the ... More
Non-invasive epicutaneous vaccine against Respiratory Syncytial Virus: Preclinical proof of concept.
AuthorsHervé PL, Descamps D, Deloizy C, Dhelft V, Laubreton D, Bouguyon E, Boukadiri A, Dubuquoy C, Larcher T, Benhamou PH, Eléouët JF, Bertho N, Mondoulet L, Riffault S
JournalJ Control Release
PubMed ID27720994
To put a Respiratory Syncytial Virus (RSV) vaccine onto the market, new vaccination strategies combining scientific and technical innovations need to be explored. Such a vaccine would also need to be adapted to the vaccination of young children that are the principal victims of acute RSV infection. In the present ... More
Contrasting Inducible Knockdown of the Auxiliary PTEX Component PTEX88 in P. falciparum and P. berghei Unmasks a Role in Parasite Virulence.
AuthorsChisholm SA, McHugh E, Lundie R, Dixon MW, Ghosh S, O'Keefe M, Tilley L, Kalanon M, de Koning-Ward TF
JournalPLoS One
PubMed ID26886275
Pathogenesis of malaria infections is linked to remodeling of erythrocytes, a process dependent on the trafficking of hundreds of parasite-derived proteins into the host erythrocyte. Recent studies have demonstrated that the Plasmodium translocon of exported proteins (PTEX) serves as the central gateway for trafficking of these proteins, as inducible knockdown ... More
CD73 regulates anti-inflammatory signaling between apoptotic cells and endotoxin-conditioned tissue macrophages.
The phagocytosis of apoptotic cells (efferocytosis) shifts macrophages to an anti-inflammatory state through a set of still poorly understood soluble and cell-bound signals. Apoptosis is a common feature of inflamed tissues, and efferocytosis by tissue macrophages is thought to promote the resolution of inflammation. However, it is not clear how ... More
Detrimental effect of systemic antimicrobial CD4
AuthorsKwong Chung CK, Ronchi F, Geuking MB
JournalImmunology
PubMed ID27779311
Healthy host-microbe mutualism relies on compartmentalization and proper regulation of systemic and mucosal immune responses. Nevertheless, the systemic immune system is frequently exposed to bouts of bacteraemia, which can trigger systemic antimicrobial immune reactivity including CD4 ... More
Therapeutic effects of a single injection of human umbilical mesenchymal stem cells on acute and chronic colitis in mice.
AuthorsChang YL, Lo HY, Cheng SP, Chang KT, Lin XF, Lee SP, Hsieh MF, Chan CK
JournalSci Rep
PubMed ID30967579
Multiple injections of bone marrow mesenchymal stem cells (BMMSCs) have been used for treatment of chronic colitis in mice. We aimed to report the therapeutic effects of a single injection of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute and chronic colitis. Male C57BL/6JNarl mice were divided into control, ... More
Infection-Induced Resistance to Experimental Cerebral Malaria Is Dependent Upon Secreted Antibody-Mediated Inhibition of Pathogenic CD8
AuthorsShaw TN, Inkson CA, Villegas-Mendez A, Pattinson DJ, Strangward P, Else KJ, Draper SJ, Zeef LAH, Couper KN
JournalFront Immunol
PubMed ID30846985
Cerebral malaria (CM) is one of the most severe complications of
Persistence of Integrase-Deficient Lentiviral Vectors Correlates with the Induction of STING-Independent CD8
AuthorsCousin C, Oberkampf M, Felix T, Rosenbaum P, Weil R, Fabrega S, Morante V, Negri D, Cara A, Dadaglio G, Leclerc C
JournalCell Rep
PubMed ID30699352
Lentiviruses are among the most promising viral vectors for in vivo gene delivery. To overcome the risk of insertional mutagenesis, integrase-deficient lentiviral vectors (IDLVs) have been developed. We show here that strong and persistent specific cytotoxic T cell (CTL) responses are induced by IDLVs, which persist several months after a single injection. ... More
Immediate Release of Gastrin-Releasing Peptide Mediates Delayed Radiation-Induced Pulmonary Fibrosis.
AuthorsTighe RM, Heck K, Soderblom E, Zhou S, Birukova A, Young K, Rouse D, Vidas J, Komforti MK, Toomey CB, Cuttitta F, Sunday ME
JournalAm J Pathol
PubMed ID30898588
Radiation-induced pulmonary fibrosis (RTPF) is a progressive, serious condition in many subjects treated for thoracic malignancies or after accidental nuclear exposure. No biomarker exists for identifying the irradiated subjects most susceptible to pulmonary fibrosis (PF). Previously, we determined that gastrin-releasing peptide (GRP) was elevated within days after birth in newborns ... More
Rational design of a live-attenuated eastern equine encephalitis virus vaccine through informed mutation of virulence determinants.
AuthorsTrobaugh DW, Sun C, Dunn MD, Reed DS, Klimstra WB
JournalPLoS Pathog
PubMed ID30742691
Live attenuated vaccines (LAVs), if sufficiently safe, provide the most potent and durable anti-pathogen responses in vaccinees with single immunizations commonly yielding lifelong immunity. Historically, viral LAVs were derived by blind passage of virulent strains in cultured cells resulting in adaptation to culture and a loss of fitness and disease-causing ... More
CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis.
AuthorsRoblek M, Protsyuk D, Becker PF, Stefanescu C, Gorzelanny C, Glaus Garzon JF, Knopfova L, Heikenwalder M, Luckow B, Schneider SW, Borsig L
JournalMol Cancer Res
PubMed ID30552233
Increased levels of the chemokine CCL2 in cancer patients are associated with poor prognosis. Experimental evidence suggests that CCL2 correlates with inflammatory monocyte recruitment and induction of vascular activation, but the functionality remains open. Here, we show that endothelial Ccr2 facilitates pulmonary metastasis using an endothelial-specific Ccr2-deficient mouse model (Ccr2 ... More
Tumor cell endogenous HIF-1a activity induces aberrant angiogenesis and interacts with TRAF6 pathway required for colorectal cancer development.
AuthorsGlaus Garzon JF, Pastrello C, Jurisica I, Hottiger MO, Wenger RH, Borsig L
JournalNeoplasia
PubMed ID33142239
Hypoxia and inflammation are key factors for colorectal cancer tumorigenesis. The colonic epithelium belongs to the tissues with the lowest partial pressure of oxygen in the body, and chronic inflammation is associated with an increased chance to develop colon cancer. How the colonic epithelium responds to hypoxia and inflammation during ... More
Artificially induced MAIT cells inhibit M. bovis BCG but not M. tuberculosis during in vivo pulmonary infection.
AuthorsYu H, Yang A, Derrick S, Mak JYW, Liu L, Fairlie DP, Cowley S
JournalSci Rep
PubMed ID32788608
There is significant interest in targeting MAIT cells with immunostimulatory agents to enhance immune responses. Mycobacterium tuberculosis (M. tb.) is a pervasive respiratory disease that could benefit from treatments that augment immunity. Here we investigate the role of MAIT cells in M. tb. infection and the potential for MAIT cell-targeted ... More
NMR Spectroscopic Windows on the Systemic Effects of SARS-CoV-2 Infection on Plasma Lipoproteins and Metabolites in Relation to Circulating Cytokines.
AuthorsLodge S, Nitschke P, Kimhofer T, Coudert JD, Begum S, Bong SH, Richards T, Edgar D, Raby E, Spraul M, Schaefer H, Lindon JC, Loo RL, Holmes E, Nicholson JK
JournalJ Proteome Res
PubMed ID33426894
To investigate the systemic metabolic effects of SARS-CoV-2 infection, we analyzed
MyD88 in myofibroblasts enhances colitis-associated tumorigenesis via promoting macrophage M2 polarization.
AuthorsYuan Q, Gu J, Zhang J, Liu S, Wang Q, Tian T, Chen Z, Zhang J
JournalCell Rep
PubMed ID33535045
The signal adaptor MyD88, an essential component of TLR signaling, plays an important role in gut-microbiome interactions. However, its contribution to colitis-associated cancer (CAC) is still controversial. Far less is known about the specific effects of MyD88 signaling in myofibroblasts in CAC development. Here, we used a CAC mouse model ... More