A commensal Clostridium species restricts alphavirus dissemination through a bile acid-type I IFN signaling axis
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PROVIDER: PRJEB38319 | ENA |
REPOSITORIES: ENA
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Project description:The emerging alphavirus chikungunya virus (CHIKV) has infected millions of people. However, the factors modulating disease outcome remain poorly understood. We show that depletion of the gut microbiota in oral antibiotic-treated or germ-free mice leads to greater CHIKV infection and spread within one day of virus inoculation. Perturbation of the gut microbiota alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single commensal bacterial species, Clostridium scindens, or its derived metabolite, the bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, commensal gut bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects virus dissemination and potentially, epidemic spread 3 biological replicates were processed per time point and group
2020-06-09 | GSE152043 | GEO
Project description:The emerging alphavirus chikungunya virus (CHIKV) has infected millions of people. However, the factors modulating disease outcome remain poorly understood. We show that depletion of the gut microbiota in oral antibiotic-treated or germ-free mice leads to greater CHIKV infection and spread within one day of virus inoculation. Perturbation of the gut microbiota alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single commensal bacterial species, Clostridium scindens, or its derived metabolite, the bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, commensal gut bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects virus dissemination and potentially, epidemic spread
2020-05-13 | GSE150387 | GEO
Project description:A commensal Clostridium bacteria restricts alphavirus dissemination through a bile acid-type I IFN signaling axis
| PRJNA638141 | ENA
Project description:A commensal Clostridium bacteria restricts alphavirus dissemination through a bile acid-type I IFN signaling axis
| PRJNA631968 | ENA
Project description:Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation. Alteration of the microbiome alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single bacterial species, Clostridium scindens, or its derived metabolite, the secondary bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, symbiotic intestinal bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects viremia, dissemination, and potentially transmission.
| S-EPMC7483520 | biostudies-literature
Project description:While viremia in the vertebrate host is a critical determinant of arboviral reservoir competency, transmission efficiency, and disease severity, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread to the bloodstream. Upon reaching the bloodstream, MARCO-expressing Kupffer cells in the liver remove circulating alphavirus particles, limiting viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus particles in the lymph node and liver has important implications as viremia and viral tissue burdens are elevated in MARCO-/- mice and disease outcomes are more severe. These findings uncover a previously unrecognized pathogen scavenging role for LECs and improve our mechanistic understanding of viremia control during arboviral infections.
2021-09-10 | GSE174667 | GEO
Project description:16S data from CHIKV infected mice under various antibiotic treatments.
| PRJEB36871 | ENA
Project description:Infection with Salmonella enterica serovar Typhi in humans causes the systemic, life-threatening disease typhoid fever. In the laboratory, typhoid fever can be modeled through the inoculation of susceptible mice with Salmonella enterica serovar Typhimurium. The ensuing disease is characterized by systemic dissemination and colonization of many organs, including the liver, spleen and gallbladder. Using this murine model, we previously characterized the interactions between Salmonella Typhimurium and host cells in the gallbladder and showed that this pathogen can successfully invade gallbladder epithelial cells and proliferate. Additionally, we showed that Salmonella Typhimurium can use bile phospholipids to grow at high rates. These abilities are likely important for quick colonization of the gallbladder during typhoid fever and further pathogen dissemination through fecal shedding. To further characterize the interactions between Salmonella and the gallbladder environment we compared the transcriptome of Salmonella cultures grown in LB or physiological murine bile. Our data showed that many genes involved in bacterial central metabolism are affected by bile, with the citric acid cycle being repressed and alternative respiratory systems being activated. Additionally, our study revealed a new aspect of Salmonella interactions with bile through the identification of phoP as a bile-responsive gene. Repression of phoP expression does not involve PhoPQ sensing of a bile component. Due to its critical role in Salmonella virulence, further studies in this area will likely reveal aspects of the interaction between Salmonella and bile that are relevant to disease.
2011-11-10 | GSE33604 | GEO
Project description:Salmon pancreas disease, caused by salmonid alphavirus (SAV), is an economically important disease affecting farmed Atlantic salmon (Salmo salar L.) in Europe, with outbreaks reported in Scotland, Norway, and Ireland. A microarray-based study was performed to evaluate the host transcriptomic response during the early stages of an experimentally induced salmonid alphavirus 1 (SAV 1) infection in Atlantic salmon (Salmo salar L.) Head kidney was sampled from five fish PD infected Atlantic salmon parr and uninfected controls on days 1, 3 and 5 post injection (d.p.i). RNA from tissue samples was amplified and interrogated using the 17k TRAITS / SGP cDNA microarray, with results validated by SYBR green real-time PCR. The greatest number of significantly differentially expressed genes was recorded on day 3 p.i. These were found to be mainly associated with immune and defence mechanisms including genes involved in interferon I & II pathways and major histocompatibility complex class I & II responses. The expression of genes associated with apoptosis (BcL2 and caspase 3/7) and cellular stress (heat shock protein) were also found to differ significantly between infected and uninfected individuals as were genes involved in inhibiting viral attachment and replication, such as ubiquitin, serum myeloid, and and viperin.
2011-06-01 | E-TABM-1060 | biostudies-arrayexpress