scholarly journals Streptococcus pneumoniae Endopeptidase O (PepO) Elicits a Strong Innate Immune Response in Mice via TLR2 and TLR4 Signaling Pathways

2016 ◽  
Vol 6 ◽  
Author(s):  
Hong Zhang ◽  
Lihua Kang ◽  
Hua Yao ◽  
Yujuan He ◽  
Xiaofang Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Signaling Pathways ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Tlr4 Signaling

scholarly journals The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

2021 ◽  
Vol 9 (6) ◽  
pp. 1324
Author(s):  
Fernanda Raya Tonetti ◽  
Mikado Tomokiyo ◽  
Ramiro Ortiz Moyano ◽  
Sandra Quilodrán-Vega ◽  
Hikari Yamamuro ◽  
...  
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Innate Immune Response ◽  
Pneumococcal Infection ◽  
Innate Immune ◽  
Nasal Administration ◽  
Commensal Bacterium ◽  
Beneficial Effects ◽  
Immunological Mechanisms ◽  
Immunomodulatory Properties

Previously, we demonstrated that the nasal administration of Dolosigranulum pigrum 040417 differentially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 2 in infant mice. In this work, we aimed to evaluate the beneficial effects of D. pigrum 040417 in the context of Streptococcus pneumoniae infection and characterize the role of alveolar macrophages (AMs) in the immunomodulatory properties of this respiratory commensal bacterium. The nasal administration of D. pigrum 040417 to infant mice significantly increased their resistance to pneumococcal infection, differentially modulated respiratory cytokines production, and reduced lung injuries. These effects were associated to the ability of the 040417 strain to modulate AMs function. Depletion of AMs significantly reduced the capacity of the 040417 strain to improve both the reduction of pathogen loads and the protection against lung tissue damage. We also demonstrated that the immunomodulatory properties of D. pigrum are strain-specific, as D. pigrum 030918 was not able to modulate respiratory immunity or to increase the resistance of mice to an S. pneumoniae infection. These findings enhanced our knowledge regarding the immunological mechanisms involved in modulation of respiratory immunity induced by beneficial respiratory commensal bacteria and suggested that particular strains could be used as next-generation probiotics.

scholarly journals Mitochondrial UPR negatively regulates wounding-induced innate immune response in C. elegans epidermis

2021 ◽  
Author(s):  
Jianzhi Zhao ◽  
Hongying Fu ◽  
Hengda Zhou ◽  
Xuecong Ren ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathways ◽  
Innate Immune Response ◽  
Tissue Damage ◽  
P38 Map Kinase ◽  
Innate Immune ◽  
Loss Of Function ◽  
C Elegans ◽  
Unfolded Protein ◽  
Protein Response

Tissue damage elicits a rapid innate immune response that is essential for efficient wound healing and survival of metazoans. It is well known that p38 MAPK kinase, TGF-β, and hemidesmosome signaling pathways have been involved in wounding-induced innate immunity in C. elegans. Here, we find that loss of function of ATFS-1 increased innate immune response while an elevated level of mitochondrial unfolded protein response (mitoUPR) inhibits the innate immune response upon epidermal wounding. Epidermal wounding triggers the nucleus export of ATFS-1 and inhibits themitoUPR in C. elegans epidermis. Moreover, genetic analysis suggests that ATFS-1 functions upstream of the p38 MAP kinase, TGF-β, and DAF-16 signaling pathways in regulating AMPs induction. Thus, our results suggest that the mitoUPR function as an intracellular signal required to fine-tune innate immune response after tissue damage.

scholarly journals Relative Contributions of the cGAS-STING and TLR3 Signaling Pathways to Attenuation of Herpes Simplex Virus 1 Replication

2020 ◽  
Vol 94 (6) ◽  
Author(s):  
Muhammad Bilal Latif ◽  
Rameez Raja ◽  
Patricia M. Kessler ◽  
Ganes C. Sen
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Innate Immune Response ◽  
Human Cell ◽  
Innate Immune ◽  
Human Cell Lines ◽  
Herpes Simplex Virus 1 ◽  
Hsv 1

ABSTRACT The innate immune response is crucial for defense against viral infections. Cells recognize virus infection through pattern recognition receptors and induce type I interferons as well as proinflammatory cytokines to orchestrate an innate immune response. Herpes simplex virus 1 (HSV-1) triggers both the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) and Toll-like receptor 3 (TLR3) pathways. It is well known that TLR3 uses the adaptor protein Toll/interleukin-1 receptor (IL-1R) domain-containing adaptor-inducing beta interferon (TRIF) for signaling, but we recently reported that STING signaling also requires TRIF. Because STING directly binds to TRIF, we identified the STING-interacting domain of TRIF and generated STING-noninteracting mutants of human and mouse TRIFs. The mutant TRIFs were unable to support STING signaling, although they were fully functional in the TLR3 pathway. These mutants were used to assess the relative contributions of the TLR3 and STING pathways to the attenuation of HSV-1 replication in mouse and human cell lines. For this purpose, the mouse L929 and NB41A3 cell lines and the human HT1080 and HeLa-M cell lines, in which both the TLR3 and the STING pathways are operational, were used. The TRIF gene was disrupted in these lines by CRISPR/Cas9, before reconstituting them with mutant and wild-type TRIF expression vectors. Infection of the reconstituted cells with HSV-1 revealed that both the cGAS-STING and the TLR3 signaling pathways are required for the attenuation of virus replication, but their relative contributions in attenuating HSV-1 replication were found to be different in mouse versus human cell lines. Thus, our study suggests that the relative contributions of the cGAS-STING and the TLR3 pathways in the attenuation of viral infection may be species specific. IMPORTANCE The magnitude of fatal infections caused by all different viruses in human and animal populations justifies a better understanding of the host innate immune response process that attenuates virus replication. In particular, the relative contributions of different signaling pathways which are responsible for the generation of the innate immune response are still largely unknown. In this study, we used STING-noninteracting TRIF mutants to decipher the relative contributions of the TLR3 and cGAS-STING signaling pathways to the attenuation of HSV-1 infection. We show that the relative contributions of the two pathways to the attenuation of viral infection are different in mouse versus human cell lines. Together, our results provide new insights into the relative contributions of two different signaling pathways in the attenuation of viral infection and may lead to the development of new antiviral strategies aimed at blocking viral infection at very early stages.

scholarly journals RIG-I-Like Receptor and Toll-Like Receptor Signaling Pathways Cause Aberrant Production of Inflammatory Cytokines/Chemokines in a Severe Fever with Thrombocytopenia Syndrome Virus Infection Mouse Model

2018 ◽  
Vol 92 (13) ◽  
pp. e02246-17 ◽  
Author(s):  
Shintaro Yamada ◽  
Masayuki Shimojima ◽  
Ryo Narita ◽  
Yuta Tsukamoto ◽  
Hiroki Kato ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Immune Response ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Tlr Signaling ◽  
Cytokines And Chemokines ◽  
Severe Fever

ABSTRACT Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a tick-borne phlebovirus of the family Bunyaviridae, SFTS virus (SFTSV). Wild-type and type I interferon (IFN-I) receptor 1-deficient (IFNAR1−/−) mice have been established as nonlethal and lethal models of SFTSV infection, respectively. However, the mechanisms of IFN-I production in vivo and the factors causing the lethal disease are not well understood. Using bone marrow-chimeric mice, we found that IFN-I signaling in hematopoietic cells was essential for survival of lethal SFTSV infection. The disruption of IFN-I signaling in hematopoietic cells allowed an increase in viral loads in serum and produced an excess of multiple inflammatory cytokines and chemokines. The production of IFN-I and inflammatory cytokines was abolished by deletion of the signaling molecules IPS-1 and MyD88, essential for retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) and Toll-like receptor (TLR) signaling, respectively. However, IPS-1−/− MyD88−/− mice exhibited resistance to lethal SFTS with a moderate viral load in serum. Taken together, these results indicate that adequate activation of RLR and TLR signaling pathways under low to moderate levels of viremia contributed to survival through the IFN-I-dependent antiviral response during SFTSV infection, whereas overactivation of these signaling pathways under high levels of viremia resulted in abnormal induction of multiple inflammatory cytokines and chemokines, causing the lethal disease. IMPORTANCE SFTSV causes a severe infectious disease in humans, with a high fatality rate of 12 to 30%. To know the pathogenesis of the virus, we need to clarify the innate immune response as a front line of defense against viral infection. Here, we report that a lethal animal model showed abnormal induction of multiple inflammatory cytokines and chemokines by an uncontrolled innate immune response, which triggered the lethal SFTS. Our findings suggest a new strategy to target inflammatory humoral factors to treat patients with severe SFTS. Furthermore, this study may help the investigation of other tick-borne viruses.

scholarly journals Skin Commensals Amplify the Innate Immune Response to Pathogens by Activation of Distinct Signaling Pathways

2011 ◽  
Vol 131 (2) ◽  
pp. 382-390 ◽  
Author(s):  
Ines Wanke ◽  
Heiko Steffen ◽  
Christina Christ ◽  
Bernhard Krismer ◽  
Friedrich Götz ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathways ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Skin Commensals

scholarly journals Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Lea-Jessica Albrecht ◽  
Simone C. Tauber ◽  
Julika Merres ◽  
Eugenia Kress ◽  
Matthias B. Stope ◽  
...  
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Tumor Necrosis Factor ◽  
Bacterial Meningitis ◽  
Innate Immune Response ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Innate Immune ◽  
Wild Type ◽  
Necrosis Factor

The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacteriumStreptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-αand the innate immune response in vivo in a model ofStreptococcus pneumoniae-induced meningitis. For the experiments IL-6−/−, TNFR1−/−, and TNFR1-IL-6−/−KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1−/−, IL-6−/−, and TNFR1-IL-6−/−mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1−/−and TNFR1-IL-6−/−mice in contrast to IL-6−/−and wild type mice. Furthermore, the increased mortality of TNFR1−/−and TNFR1-IL-6−/−mice correlated with decreased glial cell activation compared to IL-6−/−or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.

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