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

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.

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The Yin and Yang of Innate Immunity in Stroke

BioMed Research International ◽

10.1155/2014/807978 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 12

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.

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The C-terminal domain of Salmonid Alphavirus nonstructural protein 2 (nsP2) is essential and sufficient to block RIG-I pathway induction and interferon-mediated antiviral response.

Journal of Virology ◽

10.1128/jvi.01155-21 ◽

2021 ◽

Author(s):

Raphaël Jami ◽

Emilie Mérour ◽

Julie Bernard ◽

Annie Lamoureux ◽

Jean K. Millet ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Nuclear Localization ◽

Innate Immune ◽

Type I ◽

Annual Growth Rate ◽

Structural Protein ◽

Terminal Domain ◽

Nuclear Localization Sequences

Salmonid alphavirus (SAV) is an atypical alphavirus, which has a considerable impact on salmon and trout farms. Unlike other alphaviruses such as the chikungunya virus, SAV is transmitted without an arthropod vector, and does not cause cell shut-off during infection. The mechanisms by which SAV escapes the host immune system remain unknown. By studying the role of SAV proteins on the RIG-I signaling cascade, the first line of defense of the immune system during infection, we demonstrated that non-structural protein 2 (nsP2) effectively blocks the induction of type I interferon (IFN). This inhibition, independent of the protease activity carried by nsP2, occurs downstream of IRF3 which is the transcription factor allowing the activation of the IFN promoter and its expression. The inhibitory effect of nsP2 on the RIG-I pathway depends on the localization of nsP2 in the host cell nucleus which is linked to two nuclear localization sequences (NLS) located in its C-terminal part. The C-terminal domain of nsP2 by itself is sufficient and necessary to block IFN induction. Mutation of the NLS of nsP2 is deleterious to the virus. Finally, nsP2 does not interact with IRF3, indicating that its action is possible through a targeted interaction within discrete areas of chromatin, as suggested by its punctate distribution observed in the nucleus. These results therefore demonstrate a major role for nsP2 in the control by SAV of the host cell’s innate immune response. Importance The global consumption of fish continues to rise and the future demand cannot be met by capture fisheries alone due to limited stocks of wild fish. Aquaculture is currently the world’s fastest growing food production sector with an annual growth rate of 6-8 %. Recurrent outbreaks of SAV result in significant economic losses with serious environmental consequences on wild stocks. While the clinical and pathological signs of SAV infection are fairly well known, the molecular mechanisms involved are poorly described. In the present study, we focus on the non-structural protein nsP2 and characterize a specific domain containing nuclear localization sequences that are critical for the inhibition of the host innate immune response mediated by the RIG-I pathway.

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

Current Protein and Peptide Science ◽

10.2174/1389203722666210322142725 ◽

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.

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2. First responders: the innate immune response

The Immune System: A Very Short Introduction ◽

10.1093/actrade/9780198753902.003.0002 ◽

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.

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

Vaccines ◽

10.3390/vaccines8020313 ◽

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.

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The Probiotic Bacterium Lactobacillus casei Induces Activation of the Gut Mucosal Immune System through Innate Immunity

Clinical and Vaccine Immunology ◽

10.1128/cvi.13.2.219-226.2006 ◽

2006 ◽

Vol 13 (2) ◽

pp. 219-226 ◽

Cited By ~ 309

Author(s):

C. Maldonado Galdeano ◽

G. Perdigón

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Lactobacillus Casei ◽

Mononuclear Cells ◽

Immunoglobulin A ◽

Probiotic Bacterium ◽

Innate Immune ◽

Intestinal Fluids ◽

Secretory Immunoglobulin

ABSTRACT The mechanisms by which probiotic bacteria affect the immune system are unknown yet, but many of them are attributed to an increase in the innate or in the acquired immune response. To study the influence of the probiotic bacterium Lactobacillus casei in the expression of receptors involved in the innate immune response, this bacterium was orally administered to BALB/c mice. After, they were sacrificed; the small intestine and intestinal fluids were collected to measure secretory immunoglobulin A (IgA) specific for L. casei. Mononuclear cells from Peyer's patches were isolated to determine the CD-206 and TLR-2 receptors. In histological slices we determined the number of IgA+, CD4+, CD8+, and CD3+ cells and two cytokines (interleulin-5 [IL-5] and IL-6). CD-206 and TLR-2 increased with respect to the untreated control. We did not observe an increase in the T population or in the IL-5-positive cells. IgA+ cells and IL-6-producing cells increased after 7 days of L. casei administration. We did not find specific antibodies against L. casei. The main immune cells activated after oral L. casei administration were those of the innate immune response, with an increase in the specific markers of these cells (CD-206 and TLR-2), with no modification in the number of T cells.

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Loss of DNase II function in the gonad is associated with a higher expression of antimicrobial genes in Caenorhabditis elegans

Biochemical Journal ◽

10.1042/bj20150563 ◽

2015 ◽

Vol 470 (1) ◽

pp. 145-154 ◽

Cited By ~ 8

Author(s):

Hsiang Yu ◽

Huey-Jen Lai ◽

Tai-Wei Lin ◽

Chang-Shi Chen ◽

Szecheng J. Lo

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Caenorhabditis Elegans ◽

Innate Immune Response ◽

Innate Immune ◽

Dnase Ii ◽

C Elegans ◽

Elevated Expression

This study uncovered NUC-1 and CRN-7 function in germline apoptosis. Mutations of nuc-1 and crn-7 led to elevated expression of five innate-immunity-related genes and demonstrated that DNase II activity is associated with an innate immune response in C. elegans.

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A newly established in vitro culture using transgenic Drosophila reveals functional coupling between the phospholipase A2-generated fatty acid cascade and lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in insect immunity

Biochemical Journal ◽

10.1042/bj20021603 ◽

2003 ◽

Vol 371 (1) ◽

pp. 205-210 ◽

Cited By ~ 69

Author(s):

Masashi YAJIMA ◽

Masatoshi TAKADA ◽

Nahoko TAKAHASHI ◽

Haruhisa KIKUCHI ◽

Shunji NATORI ◽

...

Keyword(s):

Immune Deficiency ◽

Immune Response ◽

Innate Immunity ◽

Arachidonic Acid ◽

Fatty Acid ◽

Innate Immune Response ◽

Innate Immune ◽

Insect Immunity ◽

Imd Pathway

Innate immunity is the first line of defence against infectious micro-organisms, and the basic mechanisms of pathogen recognition and response activation are evolutionarily conserved. In mammals, the innate immune response in combination with antigen-specific recognition is required for the activation of adaptive immunity. Therefore, innate immunity is a pharmaceutical target for the development of immune regulators. Here, for the purpose of pharmaceutical screening, we established an in vitro culture based on the innate immune response of Drosophila. The in vitro system is capable of measuring lipopolysaccharide (LPS)-dependent activation of the immune deficiency (imd) pathway, which is similar to the tumour necrosis factor signalling pathway in mammals. Screening revealed that well-known inhibitors of phospholipase A2 (PLA2), dexamethasone (Dex) and p-bromophenacyl bromide (BPB) inhibit LPS-dependent activation of the imd pathway. The inhibitory effects of Dex and BPB were suppressed by the addition of an excess of three (arachidonic acid, eicosapentaenoic acid and γ-linolenic acid) of the fatty acids so far tested. Arachidonic acid, however, did not activate the imd pathway when used as the sole agonist. These findings indicate that PLA2 participates in LPS-dependent activation of the imd pathway via the generation of arachidonic acid and other mediators, but requires additional signalling from LPS stimulation. Moreover, PLA2 was activated in response to bacterial infection in Sarcophaga. These results suggest a functional link between the PLA2-generated fatty acid cascade and the LPS-stimulated imd pathway in insect immunity.

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Stenotrophomonas maltophilia flagellin induces a compartmentalized innate immune response in mouse lung

Journal of Medical Microbiology ◽

10.1099/jmm.0.020107-0 ◽

2010 ◽

Vol 59 (8) ◽

pp. 913-919 ◽

Cited By ~ 12

Author(s):

Ayaid Khadem Zgair ◽

Sanjay Chhibber

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Innate Immune Response ◽

Stenotrophomonas Maltophilia ◽

Interleukin 1 ◽

Interleukin 10 ◽

Innate Immune ◽

Mouse Lung ◽

Necrosis Factor Alpha ◽

Activated Neutrophils

Intranasal (i.n.) instillation of different amounts of purified Stenotrophomonas maltophilia flagellin preparation (1, 5 and 15 μg) in BALB/c mice stimulated a transient innate immune response in the lungs. This was characterized by infiltration of different kinds of leukocytes (neutrophils, monocytes and lymphocytes), production of various inflammatory mediators (tumour necrosis factor alpha, interleukin 1 beta, interleukin 10, nitric oxide, myeloperoxidase and malondialdehyde) and activated alveolar macrophages (AMs). The proinflammatory cytokine production resulted in accumulation of activated neutrophils and macrophages and their products following immunostimulation with flagellin. The activation of AMs by flagellin was non-specific as AMs obtained from flagellin-treated animals, even after 4 h of exposure, were found to engulf and kill S. maltophilia and Staphylococcus aureus efficiently compared to macrophages obtained from control animals. i.n. instillation of 5 μg flagellin resulted in the generation of an effective innate immunity compared to other flagellin doses. Our data provide strong evidence that S. maltophilia flagellin stimulates innate immunity in mouse lung.

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