Abstract 153: Molecular Mimicry Between Malondialdehyde and Group A Streptococcus Contribute to the Natural Selection of Conserved Innate Immune Response

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Ayelet Gonen ◽  
Jason Cole ◽  
Romulo Oliveira ◽  
Cody J Diehl ◽  
Young Sup Byun ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Natural Selection ◽  
Innate Immune Response ◽  
Group A Streptococcus ◽  
Innate Immune ◽  
Effective Response ◽  
Group A ◽  
Molecular Patterns ◽  
Selection Of

Innate immunity utilizes evolutionarily conserved pattern recognition receptors (PRRs) to provide an early and effective response against Pathogen-Associated Molecular Patterns (PAMPs) on microbial pathogens and/or against Danger Associated Molecular Patterns (DAMPs) on endogenous modified-self structures. Atherosclerosis is a chronic inflammatory disease in which lipid peroxidation is greatly increased leading to the generation of OxLDL, which contains a variety of proinflammatory oxidation-specific neoepitopes (OSE), such as phosphocholine (PC) containing oxidized phospholipids (OxPL). Our group has shown that OSEs are DAMPs, to which has evolved a concerted innate immune response mediated by PRRs. For example, CD36, CRP and IgM E06 all recognize the PC of OxPL, but also the PC on apoptotic cells as well as the PC on the cell wall of S. pneumonia (but not as part of a lipid). Accordingly, we postulated that both endogenous DAMPs and exogenous PAMPs provide natural selection for PPR responses to PC. Malondialdehyde (MDA) is another prominent OSE target of three different PRR’s: SR-A, CFH, and the IgM NAb E014. Thus, we hypothesized that EO14 should also recognize an epitope/mimotope on an infectious pathogen. We screened a pathogen library with E014 and discovered it avidly bound to group A streptococcus (GAS). Because it was known that CFH also bound to GAS, and specifically to protein M, the major virulence factor of GAS, we used GAS with and without protein M to show that E014 specifically bound to protein M. Using a series of recombinant protein M fragments, we identified a 125 aa sequence required for binding. Using a synthetic peptide array to generate 15 aa-length overlapping peptides, we identified a 24 aa mimitope that E014 bound. We subsequently showed immunological cross reactivity between GAS, Protein M, the mimotope, and MDA in vitro and in vivo in mice and humans. Further, compared to immunization of mice with protein M, immunization with MDA-LDL provided partial protection against lethal infection with GAS. These data support the hypothesis that OSE are important targets of innate immunity and both oxidative events and pathogens have contributed to the natural selection of potent, shared innate immune responses to oxidation-specific epitopes.

scholarly journals A Chemokine-Degrading Extracellular Protease Made by Group A Streptococcus Alters Pathogenesis by Enhancing Evasion of the Innate Immune Response

2008 ◽  
Vol 76 (3) ◽  
pp. 978-985 ◽  
Author(s):  
Paul Sumby ◽  
Shizhen Zhang ◽  
Adeline R. Whitney ◽  
Fabiana Falugi ◽  
Guido Grandi ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Group A Streptococcus ◽  
Cell Envelope ◽  
Innate Immune ◽  
Infection Model ◽  
Dependent Manner ◽  
Wild Type ◽  
Group A

ABSTRACT Circumvention of the host innate immune response is critical for bacterial pathogens to infect and cause disease. Here we demonstrate that the group A Streptococcus (GAS; Streptococcus pyogenes) protease SpyCEP (S. pyogenes cell envelope protease) cleaves granulocyte chemotactic protein 2 (GCP-2) and growth-related oncogene alpha (GROα), two potent chemokines made abundantly in human tonsils. Cleavage of GCP-2 and GROα by SpyCEP abrogated their abilities to prime neutrophils for activation, detrimentally altering the innate immune response. SpyCEP expression is negatively regulated by the signal transduction system CovR/S. Purified recombinant CovR bound the spyCEP gene promoter region in vitro, indicating direct regulation. Immunoreactive SpyCEP protein was present in the culture supernatants of covR/S mutant GAS strains but not in supernatants from wild-type strains. However, wild-type GAS strains do express SpyCEP, where it is localized to the cell wall. Strain MGAS2221, an organism representative of the highly virulent and globally disseminated M1T1 GAS clone, differed significantly from its isogenic spyCEP mutant derivative strain in a mouse soft tissue infection model. Interestingly, and in contrast to previous studies, the isogenic mutant strain generated lesions of larger size than those formed following infection with the parent strain. The data indicate that SpyCEP contributes to GAS virulence in a strain- and disease-dependent manner.

scholarly journals The Yin and Yang of Innate Immunity in Stroke

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaomeng Xu ◽  
Yongjun Jiang
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Ischemic Stroke ◽  
Immune System ◽  
Innate Immune Response ◽  
Time Window ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Yin And Yang ◽  
Molecular Patterns

Immune system plays an elementary role in the pathophysiological progress of ischemic stroke. It consists of innate and adaptive immune system. Activated within minutes after ischemic onset, innate immunity is responsible for the elimination of necrotic cells and tissue repair, while it is critically involved in the initiation and amplification of poststroke inflammation that amplifies ischemic damage to the brain tissue. Innate immune response requires days to be fully developed, providing a considerable time window for therapeutic intervention, suggesting prospect of novel immunomodulatory therapies against poststroke inflammation-induced brain injury. However, obstacles still exist and a comprehensive understanding of ischemic stroke and innate immune reaction is essential. In this review, we highlighted the current experimental and clinical data depicting the innate immune response following ischemic stroke, mainly focusing on the recognition of damage-associated molecular patterns, activation and recruitment of innate immune cells, and involvement of various cytokines. In addition, clinical trials targeting innate immunity were also documented regardless of the outcome, stressing the requirements for further investigation.

scholarly journals The Innate Immune Response Elicited by Group A Streptococcus Is Highly Variable among Clinical Isolates and Correlates with the emm Type

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e101464 ◽  
Author(s):  
Márcia Dinis ◽  
Céline Plainvert ◽  
Pavel Kovarik ◽  
Magalie Longo ◽  
Agnès Fouet ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Group A Streptococcus ◽  
Innate Immune ◽  
Clinical Isolates ◽  
Group A ◽  
Emm Type

scholarly journals Extracellular deoxyribonuclease made by group A Streptococcus assists pathogenesis by enhancing evasion of the innate immune response

2005 ◽  
Vol 102 (5) ◽  
pp. 1679-1684 ◽  
Author(s):  
P. Sumby ◽  
K. D. Barbian ◽  
D. J. Gardner ◽  
A. R. Whitney ◽  
D. M. Welty ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Group A Streptococcus ◽  
Innate Immune ◽  
Group A

RNA sensors as a mechanism of innate immune evasion among SARS-CoV2, HIV and Nipah viruses

2021 ◽  
Vol 22 ◽  
Author(s):  
Dalia Cicily Kattiparambil Dixon ◽  
Chameli Ratan ◽  
Bhagyalakshmi Nair ◽  
Sabitha Mangalath ◽  
Rachy Abraham ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Vaccine Development ◽  
Innate Immune ◽  
Interferon Response ◽  
Host Immune System ◽  
Type I ◽  
Adaptive Responses ◽  
Rna Sensors

: Innate immunity is the first line of defence elicited by the host immune system to fight against invading pathogens such as viruses and bacteria. From this elementary immune response, the more complex antigen-specific adaptive responses are recruited to provide a long-lasting memory against the pathogens. Innate immunity gets activated when the host cell utilizes a diverse set of receptors known as pattern recognition receptors (PRR) to recognize the viruses that have penetrated the host and respond with cellular processes like complement system, phagocytosis, cytokine release and inflammation and destruction of NK cells. Viral RNA or DNA or viral intermediate products are recognized by receptors like toll-like receptors(TLRs), nucleotide oligomerization domain(NOD)-like receptors (NLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) thereby, inducing type I interferon response (IFN) and other proinflammatory cytokines in infected cells or other immune cells. But certain viruses can evade the host innate immune response to replicate efficiently, triggering the spread of the viral infection. The present review describes the similarity in the mechanism chosen by viruses from different families -HIV, SARS-CoV2 and Nipah viruses to evade the innate immune response and how efficiently they establish the infection in the host. The review also addresses the stages of developments of various vaccines against these viral diseases and the challenges encountered by the researchers during vaccine development.

2. First responders: the innate immune response

2017 ◽  
pp. 17-29
Author(s):  
Paul Klenerman
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Acute Phase Response ◽  
First Responders ◽  
Fundamental Question ◽  
Innate Immune ◽  
Rapid Action ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

How does the immune system know when to respond? ‘First responders: the innate immune response’ considers this fundamental question that is central to understanding both normal (e.g. to infections) and abnormal (e.g. in auto-immune diseases) responses; and designing vaccines and new therapies in cancer and infectious diseases. It looks at how ‘danger’ is sensed by the immune system through pathogen-associated molecular patterns and damage-associated molecular patterns. Having been alerted, it is important that rapid action is taken to limit the spread of a pathogen. A number of responses can be initiated immediately, forming a critical part of our innate immunity, which are followed by the acute phase response.

scholarly journals Determination of the Role and Active Sites of PKC-Delta-Like from Lamprey in Innate Immunity

2019 ◽  
Vol 20 (13) ◽  
pp. 3357
Author(s):  
Yang Xu ◽  
Huan Zhao ◽  
Yang Tian ◽  
Kaixia Ren ◽  
Nan Zheng ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune System ◽  
Innate Immune Response ◽  
Active Sites ◽  
Innate Immune ◽  
Pkc Delta ◽  
Kinase C ◽  
Catalytic Fragment

Protein kinase C-δ (PKC-δ) is an important protein in the immune system of higher vertebrates. Lampreys, as the most primitive vertebrates, have a uniquevariable lymphocyte receptor (VLR) immune system. PKC-δ-like is a crucial functional gene in lampreys and is highly expressed in their immune organs. In this study, lampreys were stimulated with different immunogens, and lipopolysaccharide (LPS) was found to increase the expression of PKC-δ-like. Overexpression of PKC-δ-like could also effectively activate the innate immune response. We further demonstrated that PKC-δ-like-CF, a catalytic fragment of PKC-δ-like, is responsible for activating the innate immune response, and Thr-211, which is Thr-419 of PKC-δ-like, was confirmed to be the key site affecting PKC-δ-like-CF activity. These results indicated that PKC-δ-like from lamprey may have an important role in the innate immune response.

scholarly journals Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 313
Author(s):  
Daniel Sepulveda-Crespo ◽  
Salvador Resino ◽  
Isidoro Martinez
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Innate Immune Response ◽  
Vaccine Development ◽  
Innate Immune ◽  
World Health ◽  
Cell Immune Response ◽  
Vaccine Adjuvants

Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines. Recent studies on HCV-vaccine adjuvants have shown that the induction of a strong T- and B-cell immune response might be enhanced by choosing the right adjuvant.

Sign in / Sign up

Export Citation Format

Share Document