Lower temperatures reduce type I interferon activity and promote alphaviral arthritis.
AuthorsProw NA, Tang B, Gardner J, Le TT, Taylor A, Poo YS, Nakayama E, Hirata TDC, Nakaya HI, Slonchak A, Mukhopadhyay P, Mahalingam S, Schroder WA, Klimstra W, Suhrbier A
JournalPLoS Pathog
PubMed ID29281739
'Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, with peripheral and limb joints most commonly affected. Using a mouse model of CHIKV infection and arthritic disease, we show that CHIKV replication and the ensuing foot arthropathy were dramatically reduced when mice were ... More
Preclinical Development of a Prophylactic Neuroprotective Therapy for the Preventive Treatment of Anticipated Ischemia-Reperfusion Injury.
AuthorsBahjat FR, Alexander West G, Kohama SG, Glynn C, Urbanski HF, Hobbs TR, Earl E, Stevens SL, Stenzel-Poore MP
JournalTransl Stroke Res
PubMed ID28378315
'Ischemia-reperfusion brain injury can be iatrogenically induced secondary to life-saving procedures. Prophylactic treatment of these patients offers a promising prevention for lifelong complications. We postulate that a cytosine-guanine (CpG) oligodeoxynucleotide (ODN) can provide robust antecedent protection against cerebral ischemic injury with minimal release of pro-inflammatory cytokines, making it an ideal ... More
The Absence of Interferon-ß Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice.
'Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (PVM), the ... More
Alveolar Macrophages Can Control Respiratory Syncytial Virus Infection in the Absence of Type I Interferons.
AuthorsMakris S, Bajorek M, Culley FJ, Goritzka M, Johansson C
JournalJ Innate Immun
PubMed ID27423203
'Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections. Immunity to RSV is initiated upon detection of the virus by pattern recognition receptors, such as RIG-I-like receptors. RIG-I-like receptors signal via MAVS to induce the synthesis of proinflammatory mediators, including type I interferons (IFNs), which trigger ... More
Cytosolic Receptor Melanoma Differentiation-Associated Protein 5 Mediates Preconditioning-Induced Neuroprotection Against Cerebral Ischemic Injury.
AuthorsGesuete R, Christensen SN, Bahjat FR, Packard AE, Stevens SL, Liu M, Salazar AM, Stenzel-Poore MP
JournalStroke
PubMed ID26564103
Preconditioning with poly-l-lysine and carboxymethylcellulose (ICLC) provides robust neuroprotection from cerebral ischemia in a mouse stroke model. However, the receptor that mediates neuroprotection is unknown. As a synthetic double-stranded RNA, poly-ICLC may bind endosomal Toll-like receptor 3 or one of the cytosolic retinoic acid-inducible gene-I-like receptor family members, retinoic acid-inducible ... More
Mouse Cytomegalovirus Infection in BALB/c Mice Resembles Virus-Associated Secondary Hemophagocytic Lymphohistiocytosis and Shows a Pathogenesis Distinct from Primary Hemophagocytic Lymphohistiocytosis.
AuthorsBrisse E, Imbrechts M, Put K, Avau A, Mitera T, Berghmans N, Rutgeerts O, Waer M, Ninivaggi M, Kelchtermans H, Boon L, Snoeck R, Wouters CH, Andrei G, Matthys P
JournalJ Immunol
PubMed ID26903481
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immunological disorder that is characterized by systemic inflammation, widespread organ damage, and hypercytokinemia. Primary HLH is caused by mutations in granule-mediated cytotoxicity, whereas secondary HLH occurs, without a known genetic background, in a context of infections, malignancies, or autoimmune and autoinflammatory disorders. Clinical manifestations ... More
Both Type I and Type II Interferons Can Activate Antitumor M1 Macrophages When Combined With TLR Stimulation.
AuthorsMüller E, Speth M, Christopoulos PF, Lunde A, Avdagic A, Øynebråten I, Corthay A
JournalFront Immunol
PubMed ID30450098
Triggering or enhancing antitumor activity of tumor-associated macrophages is an attractive strategy for cancer treatment. We have previously shown that the cytokine interferon-? (IFN-?), a type II IFN, could synergize with toll-like receptor (TLR) agonists for induction of antitumor M1 macrophages. However, the toxicity of IFN-? limits its clinical use. ... More
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