Pathogen invasion changes the intestinal microbiota composition and induces innate immune responses in the zebrafish intestine

2017 ◽  
Vol 71 ◽  
pp. 35-42 ◽  
Author(s):  
Hui-Ting Yang ◽  
Song-Song Zou ◽  
Li-Juan Zhai ◽  
Yao Wang ◽  
Fu-Miao Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Innate Immune ◽  
Microbiota Composition ◽  
Innate Immune Responses ◽  
Pathogen Invasion

scholarly journals Fecal transplantation does not transfer either susceptibility or resistance to food borne listeriosis in C57BL/6 and BALB/c/By mice

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 177 ◽  
Author(s):  
Tanya Myers-Morales ◽  
Kate M Bussell ◽  
Sarah EF D'Orazio
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Intestinal Microbiota ◽  
Innate Immune ◽  
Microbiota Composition ◽  
Innate Immune Responses ◽  
Fecal Matter ◽  
Fecal Transplantation ◽  
Food Borne ◽  
Key Factor

The composition of the intestinal microbiota has wide reaching effects on the health of an individual, including the development of protective innate immune responses.  In this report, a fecal transplantation approach was used to determine whether resistance to food borne listeriosis was dependent on the murine gut microbiota.  Transplantation of BALB/c/By feces did not increase the susceptibility of C57BL/6 mice to Listeria monocytogenes infection.   Likewise, transplantation of C57BL/6 fecal matter did not enhance the resistance of BALB/c/By mice.  Thus, intestinal microbiota composition is not a key factor that confers either susceptibility or resistance to food borne listeriosis in mice.

scholarly journals Allosteric coupling between Mn2+ and dsDNA controls the catalytic efficiency and fidelity of cGAS

2020 ◽  
Vol 48 (8) ◽  
pp. 4435-4447 ◽  
Author(s):  
Richard M Hooy ◽  
Guido Massaccesi ◽  
Kimberly E Rousseau ◽  
Michael A Chattergoon ◽  
Jungsan Sohn
Keyword(s):  
Immune Responses ◽  
Catalytic Efficiency ◽  
Genotoxic Stress ◽  
Innate Immune ◽  
Activation Mechanism ◽  
Innate Immune Responses ◽  
Allosteric Coupling ◽  
Pathogen Invasion ◽  
Length Dependent Activation ◽  
Dsdna Binding

Abstract Cyclic-G/AMP (cGAMP) synthase (cGAS) triggers host innate immune responses against cytosolic double-stranded (ds)DNA arising from genotoxic stress and pathogen invasion. The canonical activation mechanism of cGAS entails dsDNA-binding and dimerization. Here, we report an unexpected activation mechanism of cGAS in which Mn2+ activates monomeric cGAS without dsDNA. Importantly, the Mn2+-mediated activation positively couples with dsDNA-dependent activation in a concerted manner. Moreover, the positive coupling between Mn2+ and dsDNA length-dependent activation requires the cognate ATP/GTP substrate pair, while negative-cooperativity suppresses Mn2+ utilization by either ATP or GTP alone. Additionally, while Mn2+ accelerates the overall catalytic activity, dsDNA length-dependent dimerization specifically accelerates the cyclization of cGAMP. Together, we demonstrate how the intrinsic allostery of cGAS efficiently yet precisely tunes its activity.

scholarly journals New Insights into the Host–Pathogen Interaction of Mycoplasma gallisepticum and Avian Metapneumovirus in Tracheal Organ Cultures of Chicken

2021 ◽  
Vol 9 (11) ◽  
pp. 2407
Author(s):  
Nancy Rüger ◽  
Hicham Sid ◽  
Jochen Meens ◽  
Michael P. Szostak ◽  
Wolfgang Baumgärtner ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mycoplasma Gallisepticum ◽  
Innate Immune ◽  
Respiratory Pathogens ◽  
Innate Immune Responses ◽  
Organ Cultures ◽  
Avian Metapneumovirus ◽  
Pathogen Invasion ◽  
Host Pathogen Interaction ◽  
Host Pathogen

Respiratory pathogens are a health threat for poultry. Co-infections lead to the exacerbation of clinical symptoms and lesions. Mycoplasma gallisepticum (M. gallispeticum) and Avian Metapneumovirus (AMPV) are two avian respiratory pathogens that co-circulate worldwide. The knowledge about the host–pathogen interaction of M. gallispeticum and AMPV in the chicken respiratory tract is limited. We aimed to investigate how co-infections affect the pathogenesis of the respiratory disease and whether the order of invading pathogens leads to changes in host–pathogen interaction. We used chicken tracheal organ cultures (TOC) to investigate pathogen invasion and replication, lesion development, and selected innate immune responses, such as interferon (IFN) α, inducible nitric oxide synthase (iNOS) and IFNλ mRNA expression levels. We performed mono-inoculations (AMPV or M. gallispeticum) or dual-inoculations in two orders with a 24-h interval between the first and second pathogen. Dual-inoculations compared to mono-inoculations resulted in more severe host reactions. Pre-infection with AMPV followed by M. gallispeticum resulted in prolonged viral replication, more significant innate immune responses, and lesions (p < 0.05). AMPV as the secondary pathogen impaired the bacterial attachment process. Consequently, the M. gallispeticum replication was delayed, the innate immune response was less pronounced, and lesions appeared later. Our results suggest a competing process in co-infections and offer new insights in disease processes.

Effects of commercial dietary prebiotic and probiotic supplements on growth, innate immune responses, and intestinal microbiota and histology of Totoaba macdonaldi

Aquaculture ◽  
2018 ◽  
Vol 491 ◽  
pp. 239-251 ◽  
Author(s):  
Mayra L. González-Félix ◽  
Delbert M. Gatlin ◽  
Perla Urquidez-Bejarano ◽  
Carolina de la Reé-Rodríguez ◽  
Lyra Duarte-Rodríguez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Totoaba Macdonaldi

scholarly journals Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Young-Su Yi ◽  
Young-Jin Son ◽  
Chongsuk Ryou ◽  
Gi-Ho Sung ◽  
Jong-Hoon Kim ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Adaptive Immune Responses ◽  
Functional Roles ◽  
Pathogen Invasion ◽  
Adaptive Immune ◽  
Biological Responses

Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases.

scholarly journals Rifaximin prevents ethanol-induced liver injury in obese KK-Ay mice through modulation of small intestinal microbiota signature

2019 ◽  
Vol 317 (5) ◽  
pp. G707-G715 ◽  
Author(s):  
Ryuta Kitagawa ◽  
Kazuyoshi Kon ◽  
Akira Uchiyama ◽  
Kumiko Arai ◽  
Shunhei Yamashina ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Immune Responses ◽  
Intestinal Microbiota ◽  
Innate Immune ◽  
Mrna Levels ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Small Intestinal ◽  
Cluster Of Differentiation ◽  
Binge Ethanol

Exacerbation of alcoholic hepatitis (AH) with comorbid metabolic syndrome is an emerging clinical problem, where microbiota plays a profound role in the pathogenesis. Here, we investigated the effect of rifaximin (RFX) on liver injury following chronic-binge ethanol (EtOH) administration in KK-Ay mice, a rodent model of metabolic syndrome. Female, 8-wk-old KK-Ay mice were fed Lieber–DeCarli diet (5% EtOH) for 10 days, following a single EtOH gavage (4 g/kg body wt). Some mice were given RFX (0.1 g/L, in liquid diet) orally. Small intestinal contents were collected from mice without binge. Intestinal microbiota was quantified using aerobic and anaerobic culturing techniques and further analyzed by 16S rRNA sequencing in detail. EtOH feeding/binge caused hepatic steatosis, oxidative stress, and induction of inflammatory cytokines in KK-Ay mice, which were markedly prevented by RFX treatment. Hepatic mRNA levels for cluster of differentiation 14, Toll-like receptor (TLR) 4, TLR2, and NADPH oxidase 2 were increased following EtOH feeding/binge, and administration of RFX completely suppressed their increase. The net amount of small intestinal bacteria was increased over threefold after chronic EtOH feeding as expected; however, RFX did not prevent this net increase. Intriguingly, the profile of small intestinal microbiota was dramatically changed following EtOH feeding in the order level, where the Erysipelotrichales predominated in the relative abundance. In sharp contrast, RFX drastically blunted the EtOH-induced increases in the Erysipelotrichales almost completely, with increased proportion of the Bacteroidales. In conclusion, RFX prevents AH through modulation of small intestinal microbiota/innate immune responses in obese KK-Ay mice. NEW & NOTEWORTHY Here we demonstrated that rifaximin (RFX) prevents chronic-binge ethanol (EtOH)-induced steatohepatitis in KK-Ay mice. Chronic EtOH feeding caused small intestinal bacterial overgrowth, with drastic alteration in the microbiota profile predominating the order Erysipelotrichales. RFX minimized this EtOH induction in Erysipelotrichales with substitutive increases in Bacteroidales. RFX also prevented EtOH-induced increases in portal lipopolysaccharide, and hepatic cluster of differentiation 14, toll-like receptor (TLR) 2, and TLR4 mRNA levels, suggesting the potential involvement of microbiota-related innate immune responses.

scholarly journals PPP6C Negatively Regulates STING-Dependent Innate Immune Responses

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Guoxin Ni ◽  
Zhe Ma ◽  
Jason P. Wong ◽  
Zhigang Zhang ◽  
Emily Cousins ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Negative Regulator ◽  
Host Cells ◽  
Type I ◽  
Innate Immune Responses ◽  
Pathogen Invasion ◽  
Major Player ◽  
Sting Pathway

ABSTRACT Stimulator of interferon genes (STING) is an essential adaptor protein of the innate DNA-sensing signaling pathway, which recognizes genomic DNA from invading pathogens to establish antiviral responses in host cells. STING activity is tightly regulated by several posttranslational modifications, including phosphorylation. However, specifically how the phosphorylation status of STING is modulated by kinases and phosphatases remains to be fully elucidated. In this study, we identified protein phosphatase 6 catalytic subunit (PPP6C) as a binding partner of Kaposi’s sarcoma-associated herpesvirus (KSHV) open reading frame 48 (ORF48), which is a negative regulator of the cyclic GMP-AMP synthase (cGAS)-STING pathway. PPP6C depletion enhances double-stranded DNA (dsDNA)-induced and 5′ppp double-stranded RNA (dsRNA)-induced but not poly(I:C)-induced innate immune responses. PPP6C negatively regulates dsDNA-induced IRF3 activation but not NF-κB activation. Deficiency of PPP6C greatly inhibits the replication of herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) as well as the reactivation of KSHV, due to increased type I interferon production. We further demonstrated that PPP6C interacts with STING and that loss of PPP6C enhances STING phosphorylation. These data demonstrate the important role of PPP6C in regulating STING phosphorylation and activation, which provides an additional mechanism by which the host responds to viral infection. IMPORTANCE Cytosolic DNA, which usually comes from invading microbes, is a dangerous signal to the host. The cGAS-STING pathway is the major player that detects cytosolic DNA and then evokes the innate immune response. As an adaptor protein, STING plays a central role in controlling activation of the cGAS-STING pathway. Although transient activation of STING is essential to trigger the host defense during pathogen invasion, chronic STING activation has been shown to be associated with several autoinflammatory diseases. Here, we report that PPP6C negatively regulates the cGAS-STING pathway by removing STING phosphorylation, which is required for its activation. Dephosphorylation of STING by PPP6C helps prevent the sustained production of STING-dependent cytokines, which would otherwise lead to severe autoimmune disorders. This work provides additional mechanisms on the regulation of STING activity and might facilitate the development of novel therapeutics designed to prevent a variety of autoinflammatory disorders.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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