scholarly journals Temporal Analysis of Borrelia burgdorferiErp Protein Expression throughout the Mammal-Tick InfectiousCycle

2003 ◽  
Vol 71 (12) ◽  
pp. 6943-6952 ◽  
Author(s):  
Jennifer C. Miller ◽  
Kate von Lackum ◽  
Kelly Babb ◽  
Jason D. McAlister ◽  
Brian Stevenson
Keyword(s):  
Temporal Analysis ◽  
Factor H ◽  
Innate Immune ◽  
Surface Proteins ◽  
Host Immune System ◽  
Innate Immune Responses ◽  
Outer Surface Proteins ◽  
Mammalian Infection ◽  
Infectious Cycle

ABSTRACT Previous immunological studies indicated that the Lyme disease spirochete, Borrelia burgdorferi, expresses Erp outer surface proteins during mammalian infection. We conducted analyses of Erp expression throughout the entire tick-mammal infectious cycle, which revealed that the bacteria regulate Erp production in vivo. Bacteria within unfed nymphal ticks expressed little to no Erp proteins. However, as infected ticks fed on mice, B. burgdorferi increased production of Erp proteins, with essentially all transmitted bacteria expressing these proteins. Mice infected with B. burgdorferi mounted rapid IgM responses to all tested Erp proteins, followed by strong immunoglobulin G responses that generally increased in intensity throughout 11 months of infection, suggesting continued exposure of Erp proteins to the host immune system throughout chronic infection. As naive tick larvae acquired B. burgdorferi by feeding on infected mice, essentially all transmitted bacteria produced Erp proteins, also suggestive of continual Erp expression during mammalian infection. Shortly after the larvae acquired bacteria, Erp production was drastically downregulated. The expression of Erp proteins on B. burgdorferi throughout mammalian infection is consistent with their hypothesized function as factor H-binding proteins that protect the bacteria from host innate immune responses.

scholarly journals Evolutionary and structural analysis of SARS-CoV-2 specific evasion of host immunity

2020 ◽  
Vol 21 (6-8) ◽  
pp. 409-419
Author(s):  
Irfan Hussain ◽  
Nashaiman Pervaiz ◽  
Abbas Khan ◽  
Shoaib Saleem ◽  
Huma Shireen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nonstructural Protein ◽  
Critical Role ◽  
Clinical Manifestations ◽  
Host Immunity ◽  
Innate Immune ◽  
Host Immune System ◽  
Innate Immune Responses ◽  
In Vivo Models

AbstractThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading fast worldwide. There is a pressing need to understand how the virus counteracts host innate immune responses. Deleterious clinical manifestations of coronaviruses have been associated with virus-induced direct dysregulation of innate immune responses occurring via viral macrodomains located within nonstructural protein-3 (Nsp3). However, no substantial information is available concerning the relationship of macrodomains to the unusually high pathogenicity of SARS-CoV-2. Here, we show that structural evolution of macrodomains may impart a critical role to the unique pathogenicity of SARS-CoV-2. Using sequence, structural, and phylogenetic analysis, we identify a specific set of historical substitutions that recapitulate the evolution of the macrodomains that counteract host immune response. These evolutionary substitutions may alter and reposition the secondary structural elements to create new intra-protein contacts and, thereby, may enhance the ability of SARS-CoV-2 to inhibit host immunity. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection‐driven epistasis in protein evolution. Our findings warrant further characterization of macrodomain-specific evolutionary substitutions in in vitro and in vivo models to determine their inhibitory effects on the host immune system.

scholarly journals High-Resolution Profiling of Innate Immune Responses by Porcine Dendritic Cell Subsets in vitro and in vivo

2020 ◽  
Vol 11 ◽  
Author(s):  
Gaël Auray ◽  
Stephanie C. Talker ◽  
Irene Keller ◽  
Sylvie Python ◽  
Markus Gerber ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
High Resolution ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Dendritic Cell Subsets

scholarly journals Influenza Hemagglutinin and Neuraminidase: Yin–Yang Proteins Coevolving to Thwart Immunity

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 346 ◽  
Author(s):  
Ivan Kosik ◽  
Jonathan W. Yewdell
Keyword(s):  
Influenza A ◽  
Antigenic Variation ◽  
Innate Immune ◽  
Viral Fitness ◽  
Adaptive Immune ◽  
Influenza Hemagglutinin ◽  
Immune Pressure ◽  
Virion Release ◽  
Infectious Cycle

Influenza A virions possess two surface glycoproteins—the hemagglutinin (HA) and neuraminidase (NA)—which exert opposite functions. HA attaches virions to cells by binding to terminal sialic acid residues on glycoproteins/glycolipids to initiate the infectious cycle, while NA cleaves terminal sialic acids, releasing virions to complete the infectious cycle. Antibodies specific for HA or NA can protect experimental animals from IAV pathogenesis and drive antigenic variation in their target epitopes that impairs vaccine effectiveness in humans. Here, we review progress in understanding HA/NA co-evolution as each acquires epistatic mutations to restore viral fitness to mutants selected in the other protein by host innate or adaptive immune pressure. We also discuss recent exciting findings that antibodies to HA can function in vivo by blocking NA enzyme activity to prevent nascent virion release and enhance Fc receptor-based activation of innate immune cells.

194 A Non-Gluten Component of Wheat is a Strong Stimulator of Innate Immune Responses In Vitro and In Vivo and Acts via Toll Like Receptor 4

2010 ◽  
Vol 138 (5) ◽  
pp. S-36
Author(s):  
Yvonne Junker ◽  
Donatella Barisani ◽  
Daniel A. Leffler ◽  
Towia Libermann ◽  
Simon T. Dillon ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals Borrelia burgdorferi Infection-Associated Surface Proteins ErpP, ErpA, and ErpC Bind Human Plasminogen

2008 ◽  
Vol 77 (1) ◽  
pp. 300-306 ◽  
Author(s):  
Catherine A. Brissette ◽  
Katrin Haupt ◽  
Diana Barthel ◽  
Anne E. Cooley ◽  
Amy Bowman ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Critical Role ◽  
Aminocaproic Acid ◽  
Factor H ◽  
Surface Proteins ◽  
Primary Role ◽  
Dependent Manner ◽  
Lysine Residues ◽  
Complement Regulator ◽  
Mammalian Infection

ABSTRACT Host-derived plasmin plays a critical role in mammalian infection by Borrelia burgdorferi. The Lyme disease spirochete expresses several plasminogen-binding proteins. Bound plasminogen is converted to the serine protease plasmin and thereby may facilitate the bacterium's dissemination throughout the host by degrading extracellular matrix. In this work, we demonstrate plasminogen binding by three highly similar borrelial outer surface proteins, ErpP, ErpA, and ErpC, all of which are expressed during mammalian infection. Extensive characterization of ErpP demonstrated that this protein bound in a dose-dependent manner to lysine binding site I of plasminogen. Removal of three lysine residues from the carboxy terminus of ErpP significantly reduced binding of plasminogen, and the presence of a lysine analog, ε-aminocaproic acid, inhibited the ErpP-plasminogen interaction, thus strongly pointing to a primary role for lysine residues in plasminogen binding. Ionic interactions are not required in ErpP binding of plasminogen, as addition of excess NaCl or the polyanion heparin did not have any significant effect on binding. Plasminogen bound to ErpP could be converted to the active enzyme, plasmin. The three plasminogen-binding Erp proteins can also bind the host complement regulator factor H. Plasminogen and factor H bound simultaneously and did not compete for binding to ErpP, indicating separate binding sites for both host ligands and the ability of the borrelial surface proteins to bind both host proteins.

scholarly journals The Distinct Immune-Stimulatory Capacities of Porphyromonas gingivalis Strains 381 and ATCC 33277 Are Determined by the fimB Allele and Gingipain Activity

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Stephen R. Coats ◽  
Nutthapong Kantrong ◽  
Thao T. To ◽  
Sumita Jain ◽  
Caroline A. Genco ◽  
...  
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Host Cell ◽  
Porphyromonas Gingivalis ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Innate Immune ◽  
Surface Proteins ◽  
Innate Immune Responses ◽  
Content Type

ABSTRACT The Porphyromonas gingivalis strain ATCC 33277 (33277) and 381 genomes are nearly identical. However, strain 33277 displays a significantly diminished capacity to stimulate host cell Toll-like receptor 2 (TLR2)-dependent signaling and interleukin-1β (IL-1β) production relative to 381, suggesting that there are strain-specific differences in one or more bacterial immune-modulatory factors. Genomic sequencing identified a single nucleotide polymorphism in the 33277 fimB allele (A→T), creating a premature stop codon in the 33277 fimB open reading frame relative to the 381 fimB allele. Gene exchange experiments established that the 33277 fimB allele reduces the immune-stimulatory capacity of this strain. Transcriptome comparisons revealed that multiple genes related to carboxy-terminal domain (CTD) family proteins, including the gingipains, were upregulated in 33277 relative to 381. A gingipain substrate degradation assay demonstrated that cell surface gingipain activity is higher in 33277, and an isogenic mutant strain deficient for the gingipains exhibited an increased ability to induce TLR2 signaling and IL-1β production. Furthermore, 33277 and 381 mutant strains lacking CTD cell surface proteins were more immune-stimulatory than the parental wild-type strains, consistent with an immune-suppressive role for the gingipains. Our data show that the combination of an intact fimB allele and limited cell surface gingipain activity in P. gingivalis 381 renders this strain more immune-stimulatory. Conversely, a defective fimB allele and high-level cell surface gingipain activity reduce the capacity of P. gingivalis 33277 to stimulate host cell innate immune responses. In summary, genomic and transcriptomic comparisons identified key virulence characteristics that confer divergent host cell innate immune responses to these highly related P. gingivalis strains.

scholarly journals APOε4 is associated with enhanced in vivo innate immune responses in human subjects

2014 ◽  
Vol 134 (1) ◽  
pp. 127-134.e9 ◽  
Author(s):  
Stephen C. Gale ◽  
Li Gao ◽  
Carmen Mikacenic ◽  
Susette M. Coyle ◽  
Nicholas Rafaels ◽  
...  
Keyword(s):  
Immune Responses ◽  
Human Subjects ◽  
Innate Immune ◽  
Innate Immune Responses

Leishmanial apolipoprotein A-I expression: a possible strategy used by the parasite to evade the host’s immune response

2021 ◽  
Author(s):  
Kurosh Kalantar ◽  
Raúl Manzano-Román ◽  
Esmaeel Ghani ◽  
Reza Mansouri ◽  
Gholamreza Hatam ◽  
...  
Keyword(s):  
Immune System ◽  
Molecular Mimicry ◽  
Innate Immune ◽  
Host Immune System ◽  
Innate Immune Responses ◽  
Multiple Strategies ◽  
Apolipoprotein A ◽  
Trypanosome Lytic Factor ◽  
Main Component ◽  
Leishmania Parasites

Apolipoprotein A-I (apo A-I) represents the main component of the Trypanosome lytic factor (TLF) which contributes to the host innate immunity against Trypanosoma and Leishmania. These parasites use complex and multiple strategies such as molecular mimicry to evade or subvert the host immune system. Previous studies have highlighted the adaptation mechanisms of TLF-resistant Trypanosoma species. These data might support the hypothesis that Leishmania parasites (amastigote forms in macrophages) might express apo A-I to bypass and escape from TLF action as a component of the host innate immune responses. The anti-inflammatory property of apo A-I is another mechanism that supports our idea that apo A-I may play a role in Leishmania parasites allowing them to bypass the host innate immune system.

scholarly journals Polysaccharides derived from Yamoa™ (Funtumia elastica) prime γδ T cells in vitro and enhance innate immune responses in vivo

2009 ◽  
Vol 9 (11) ◽  
pp. 1313-1322 ◽  
Author(s):  
Jill C. Graff ◽  
Emily M. Kimmel ◽  
Brett Freedman ◽  
Igor A. Schepetkin ◽  
Jeff Holderness ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Γδ T Cells ◽  
Innate Immune ◽  
Innate Immune Responses

scholarly journals IFNα and IFNγ Impede Marek’s Disease Progression

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1103 ◽  
Author(s):  
Luca D. Bertzbach ◽  
Olof Harlin ◽  
Sonja Härtle ◽  
Frank Fehler ◽  
Tereza Vychodil ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Onset ◽  
Antiviral Effect ◽  
Lymphoproliferative Disease ◽  
Innate Immune ◽  
Marek's Disease ◽  
Marek’S Disease ◽  
Innate Immune Responses

Marek’s disease virus (MDV) is an alphaherpesvirus that causes Marek’s disease, a malignant lymphoproliferative disease of domestic chickens. While MDV vaccines protect animals from clinical disease, they do not provide sterilizing immunity and allow field strains to circulate and evolve in vaccinated flocks. Therefore, there is a need for improved vaccines and for a better understanding of innate and adaptive immune responses against MDV infections. Interferons (IFNs) play important roles in the innate immune defenses against viruses and induce upregulation of a cellular antiviral state. In this report, we quantified the potent antiviral effect of IFNα and IFNγ against MDV infections in vitro. Moreover, we demonstrate that both cytokines can delay Marek’s disease onset and progression in vivo. Additionally, blocking of endogenous IFNα using a specific monoclonal antibody, in turn, accelerated disease. In summary, our data reveal the effects of IFNα and IFNγ on MDV infection and improve our understanding of innate immune responses against this oncogenic virus.

Sign in / Sign up

Export Citation Format

Share Document