scholarly journals Fetal and Maternal Innate Immunity Receptors Have Opposing Effects on the Severity of Experimental Malaria in Pregnancy: Beneficial Roles for Fetus-Derived Toll-Like Receptor 4 and Type I Interferon Receptor 1

2018 ◽  
Vol 86 (5) ◽  
Author(s):  
Lurdes Rodrigues-Duarte ◽  
Yash Pandya ◽  
Rita Neres ◽  
Carlos Penha-Gonçalves
Keyword(s):  
Innate Immunity ◽  
Type I Interferon ◽  
Parasite Burden ◽  
Innate Immune ◽  
Malaria In Pregnancy ◽  
Type I ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Interferon Receptor ◽  
In Pregnancy

ABSTRACTMalaria in pregnancy (MiP) is a distinctive clinical form ofPlasmodiuminfection and is a cause of placental insufficiency leading to poor pregnancy outcomes. Maternal innate immunity responses play a decisive role in the development of placental inflammation, but the action of fetus-derived factors in MiP outcomes has been overlooked. We investigated the role of theTlr4andIfnar1genes, taking advantage of heterogenic mating strategies to dissect the effects mediated by maternally and fetally derived Toll-like receptor 4 (TLR4) or type I interferon receptor 1 (IFNAR1). Using a mouse infection system displaying severe MiP outcomes, we found that the expressions of TLR4 and IFNAR1 in the maternal compartment take part in deleterious MiP outcomes, but their fetal counterparts patently counteract these effects. We uncovered that fetal TLR4 contributes to thein vitrouptake of infected erythrocytes by trophoblasts and to the innate immune response in the placenta, offering robust protection of fetus viability, but had no sensible impact on the placental parasite burden. In contrast, we observed that the expression of IFNAR1 in the fetal compartment was associated with a reduced placental parasite burden but had little beneficial effect on fetus outcomes. Furthermore, the downregulation ofIfnar1expression in infected placentas and in trophoblasts exposed to infected erythrocytes indicated that the interferon-IFNAR1 pathway is involved in the trophoblast response to infection. This work unravels that maternal and fetal counterparts of innate immune pathways drive opposing responses in murine placental malaria and implicates the activation of innate receptors in fetal trophoblast cells in the control of placental infection and in the protection of the fetus.

Abstract 291: The Type I Interferon Receptor Amplifies Innate Immune Responses After Myocardial Infarction

2018 ◽  
Vol 123 (Suppl_1) ◽  
Author(s):  
Richard P Ng ◽  
Kevin R King ◽  
Aaron D Aguirre ◽  
Sean P Arlauckas ◽  
Ralph Weissleder
Keyword(s):  
Myocardial Infarction ◽  
Immune Responses ◽  
Type I Interferon ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Interferon Receptor

scholarly journals Type I interferon signaling contributes to the bias that Toll-like receptor 4 exhibits for signaling mediated by the adaptor protein TRIF

2014 ◽  
Vol 7 (351) ◽  
pp. ra108-ra108 ◽  
Author(s):  
J. P. Kolb ◽  
C. R. Casella ◽  
S. SenGupta ◽  
P. M. Chilton ◽  
T. C. Mitchell
Keyword(s):  
Type I Interferon ◽  
Adaptor Protein ◽  
Type I ◽  
Interferon Signaling ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals Boosting Toll-like receptor 4 signaling enhances the therapeutic outcome of antibiotic therapy in pneumococcal pneumonia

2020 ◽  
Author(s):  
Fiordiligie Casilag ◽  
Sebastian Franck ◽  
Laura Matarazzo ◽  
Martin Figeac ◽  
Robin Michelet ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Antibiotic Therapy ◽  
Lung Tissue ◽  
Bacterial Load ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Term Survival ◽  
Monophosphoryl Lipid A ◽  
Host Innate Immunity

ABSTRACTThe emergence and spread of antibiotic resistance emphasize the need for alternative treatment strategies against bacterial infections. Boosting the host innate immunity is not only readily deployable in most individuals but can also mobilize many different antibacterial defenses. This study tested the hypothesis whereby stimulation of the innate immune receptor Toll-like receptor 4 (TLR4) can be combined with antibiotics in the treatment of invasive pneumonia. In a mouse model of Streptococcus pneumoniae infection, a single oral administration of low-dose amoxicillin (AMX) or the systemic delivery of monophosphoryl lipid A (MPLA, a clinically-approved TLR4 activator) decreased the bacterial load in lung and spleen, although this was not sufficient for long-term survival. In contrast, a single treatment with a combination of MPLA and AMX induced significant bacterial clearance with little to no regrowth over time, and was associated with longer survival. Upregulation of genes related to granulocyte infiltration in lung tissue and elevation of blood levels of pro-inflammatory cytokines was immediate and transient in MPLA-treated mice; this indicates activation of the innate immune system in a context of infection. Combination treatment was associated with a well-preserved lung tissue architecture and more rapid recovery from inflammation - suggesting that immune activation by MPLA does not exacerbate pneumonia-induced damage. After AMX administration, plasma AMX concentrations rapidly reached the maximum and declined, whereas the downstream effects of MPLA extended beyond AMX elimination; these findings suggested a two-step effect. Our results demonstrated that leveraging host innate immunity increases the efficacy of antibiotic therapy in bacterial pneumonia.

scholarly journals Type I Interferon Induction by Neisseria gonorrhoeae: Dual Requirement of Cyclic GMP-AMP Synthase and Toll-like Receptor 4

Cell Reports ◽  
2016 ◽  
Vol 15 (11) ◽  
pp. 2438-2448 ◽  
Author(s):  
Warrison A. Andrade ◽  
Sarika Agarwal ◽  
Shunyan Mo ◽  
Scott A. Shaffer ◽  
Joseph P. Dillard ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Cyclic Gmp ◽  
Type I Interferon ◽  
Type I ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Interferon Induction

scholarly journals The Intestinal Microbiome Primes Host Innate Immunity against Enteric Virus Systemic Infection through Type I Interferon

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Xiao-Lian Yang ◽  
Gan Wang ◽  
Jin-Yan Xie ◽  
Han Li ◽  
Shu-Xian Chen ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Type I Interferon ◽  
Systemic Infection ◽  
Enteric Virus ◽  
Innate Immune ◽  
Commensal Bacteria ◽  
Type I ◽  
Innate Immune Responses ◽  
Host Innate Immunity

ABSTRACT Intestinal microbiomes are of vital importance in antagonizing systemic viral infection. However, very little literature has shown whether commensal bacteria play a crucial role in protecting against enteric virus systemic infection from the aspect of modulating host innate immunity. In the present study, we utilized an enteric virus, encephalomyocarditis virus (EMCV), to inoculate mice treated with phosphate-buffered saline (PBS) or given an antibiotic cocktail (Abx) orally or intraperitoneally to examine the impact of microbiota depletion on virulence and viral replication in vivo. Microbiota depletion exacerbated the mortality, neuropathogenesis, viremia, and viral burden in brains following EMCV infection. Furthermore, Abx-treated mice exhibited severely diminished mononuclear phagocyte activation and impaired type I interferon (IFN) production and expression of IFN-stimulated genes (ISG) in peripheral blood mononuclear cells (PBMC), spleens, and brains. With the help of fecal bacterial 16S rRNA sequencing of PBS- and Abx-treated mice, we identified a single commensal bacterium, Blautia coccoides, that can restore mononuclear phagocyte- and IFNAR (IFN-α/β receptor)-dependent type I IFN responses to restrict systemic enteric virus infection. These findings may provide insight into the development of novel therapeutics for preventing enteric virus infection or possibly alleviating clinical diseases by activating host systemic innate immune responses via respective probiotic treatment using B. coccoides. IMPORTANCE While cumulative data indicate that indigenous commensal bacteria can facilitate enteric virus infection, little is known regarding whether intestinal microbes have a protective role in antagonizing enteric systemic infection by modulating host innate immunity. Although accumulating literature has pointed out that the microbiota has a fundamental impact on host systemic antiviral innate immune responses mediated by type I interferon (IFN), only a few specific commensal bacteria species have been revealed to be capable of regulating IFN-I and ISG expression, not to mention the underlying mechanisms. Thus, it is important to understand the cross talk between microbiota and host anti-enteric virus innate immune responses and characterize the specific bacterial species that possess protective functions. Our study demonstrates how fundamental innate immune mediators such as mononuclear phagocytes and type I IFN are regulated by commensal bacteria to antagonize enteric virus systemic infection. In particular, we have identified a novel commensal bacterium, Blautia coccoides, that can restrict enteric virus replication and neuropathogenesis by activating IFN-I and ISG responses in mononuclear phagocytes via an IFNAR- and STAT1-mediated signaling pathway.

scholarly journals STAT2 Mediates Innate Immunity to Dengue Virus in the Absence of STAT1 via the Type I Interferon Receptor

2011 ◽  
Vol 7 (2) ◽  
pp. e1001297 ◽  
Author(s):  
Stuart T. Perry ◽  
Michael D. Buck ◽  
Steven M. Lada ◽  
Christian Schindler ◽  
Sujan Shresta
Keyword(s):  
Innate Immunity ◽  
Dengue Virus ◽  
Type I Interferon ◽  
Type I ◽  
Interferon Receptor

scholarly journals Prothymosin-  inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction

2010 ◽  
Vol 107 (22) ◽  
pp. 10178-10183 ◽  
Author(s):  
A. Mosoian ◽  
A. Teixeira ◽  
C. S. Burns ◽  
L. E. Sander ◽  
G. L. Gusella ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Interferon Induction ◽  
Hiv 1
Sign in / Sign up

Export Citation Format

Share Document