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Journal of Hepatology Jun 2024Gut bacterial translocation contributes to immune dysfunction and spontaneous bacterial peritonitis (SBP) in cirrhosis. We hypothesized that exposure of peritoneal...
BACKGROUND & AIMS
Gut bacterial translocation contributes to immune dysfunction and spontaneous bacterial peritonitis (SBP) in cirrhosis. We hypothesized that exposure of peritoneal macrophages (PMs) to bacterial DNA results in type-I interferon (IFN) production, shaping subsequent immune responses, inflammasome activation, and the release of damage-associated molecular patterns (DAMPs).
METHODS
PMs from patients with cirrhosis were stimulated with E. coli single-stranded DNA (ssDNA), lipopolysaccharide LPS, and IFN or infected with E. coli, S. aureus, and Group B streptococcus in vitro. Cytokine release, inflammasome activation, and DAMP release were quantified by quantitative-PCR, ELISA, western blots, and reporter cells employing primary PMs, monocytes, and caspase-deficient THP-1 macrophages. Serum progranulin concentration was correlated with transplant-free survival in 77 patients with SBP.
RESULTS
E. coli ssDNA induced strong type-I IFN activity in PMs and monocytes, priming them for enhanced LPS-mediated tumor necrosis factor production without toll-like receptor 4 tolerance induction. During in vitro macrophage bacterial infection, type-I IFN release aligned with upregulated expression of IFN-regulatory factors (IRF)1/2 and guanylate binding proteins (GBP)2/5. PMs upregulated inflammasome-associated proteins and type-I IFN upon E. coli ssDNA exposure and released interleukin-1β upon bacterial infection. Proteomic screen in mouse macrophages revealed progranulin as being caspase-11-dependent during E. coli infection. PMs and THP-1 macrophages released significant amounts of progranulin when infected with S. aureus or E. coli via gasdermin-D in a type-I IFN and caspase-5-dependent manner. During SBP, PMs upregulated IRF1, GBP2/5 and caspase-5 and higher serum progranulin concentrations were indicative of lower 90-day transplant-free survival after SBP.
CONCLUSIONS
Type-I IFN shapes peritoneal immune responses and regulates caspase-5-mediated progranulin release during SBP.
IMPACT AND IMPLICATIONS
Patients with cirrhosis exhibit impaired immune responses and increased susceptibility to bacterial infections. This study reveals that type-I interferon responses, triggered by pathogen-associated molecular patterns, are crucial in regulating macrophage activation and priming them for inflammatory responses. Additionally, we elucidate the mechanisms by which type-I interferons promote the release of progranulin from macrophages during spontaneous bacterial peritonitis. Our findings enhance understanding of how bacterial translocation affects immune responses, identify novel biomarkers for inflammasome activation during infections, and point to potential therapeutic targets.
PubMed: 38936554
DOI: 10.1016/j.jhep.2024.06.019 -
MSystems Jun 2024(), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and...
UNLABELLED
(), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and host health or diseases has received increasing attention. However, the role of gut microbiota in the process of infection is still unclear. In this study, we established a infection model in C57BL/6 mice and examined the impact of preemptive oral administration () on infection. Our findings revealed that infection led to pronounced pathological alterations in the liver and kidneys, characterized by abscess formation, intense inflammatory responses, and bacterial overload. Remarkably, these deleterious effects were greatly relieved by oral administration of before infection with . Additionally, we further found that during infection, peritoneal macrophages (PMs) of mice orally administered with accumulated more rapidly at sites of infection. Furthermore, our results showed that PMs from mice with oral administration showed a stronger clearance effect, and this was mediated by high expression of LC3-II protein. Meanwhile, oral administration of protected the gut microbiota disorder in C57BL/6 mice caused by infection. In summary, our study demonstrates that oral administration of confers effective protection against infection in C57BL/6 mice by modulating macrophage autophagy, thereby augmenting bacterial clearance and preserving gut microbiota and function stability. These findings position as a viable probiotic candidate for the clinical prevention of infection.
IMPORTANCE
(C. ) is known to induce a range of chronic diseases in both animals and humans. Currently, clinical treatment for C. infection mainly relies on antibiotic therapy or surgical intervention. However, excessive use of antibiotics may increase the risk of drug-resistant strains, and the effectiveness of treatment remains unsatisfactory. Furthermore, surgical procedures do not completely eradicate pathogens and can easily cause environmental pollution. Probiotic interventions are receiving increasing attention for improving the body's immune system and maintaining health. In this study, we established a C. infection model in C57BL/6 mice to explore the impact of acidophilus during C. infection. Our results showed that effectively protected against C. infection by regulating the autophagy of macrophages and maintaining intestinal microbiota homeostasis. This study may provide a new strategy for the prevention of C. infection.
PubMed: 38934644
DOI: 10.1128/msystems.00484-24 -
Kidney Research and Clinical Practice May 2024Patients with end-stage kidney disease (ESKD) are more susceptible to viral epidemics and are known to have higher incidence and death rates of coronavirus disease 2019...
BACKGROUND
Patients with end-stage kidney disease (ESKD) are more susceptible to viral epidemics and are known to have higher incidence and death rates of coronavirus disease 2019 (COVID-19) compared to the general population. We determined COVID-19 incidence and mortality among chronic hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT) patients in Korea.
METHODS
We conducted a retrospective cohort study and data regarding Korean ESKD adults (aged ≥18 years) were obtained from the National Health Insurance Service of Korea from October 2020 to December 2021. We examined and compared the incidence of COVID-19-related infections and deaths among the patients receiving HD, PD, and KT.
RESULTS
Of all ESKD patients, 85,018 (68.1%) were on HD, 8,399 (6.7%) on PD, and 31,343 (25.1%) on KT. The COVID-19 incidence was 1.3% for HD, 1.2% for PD, and 1.5% for KT. COVID-19 mortality was 16.3% for HD, 12.2% for PD, and 4.7% for KT. PD patients had a lower incidence of infection compared to HD patients (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.607-0.93), but KT patients had a significantly higher risk of infection (OR, 1.28; 95% CI, 1.13-1.44). Compared with HD, the risk of COVID-19-related death was not different for PD patients but was significantly lower for KT patients (hazard ratio, 0.55; 95% CI, 0.35-0.88).
CONCLUSION
COVID-19 incidence was lower in PD patients than in HD patients, but mortality was not different between them. KT was associated with a higher risk of COVID-19 infection but lower mortality compared to HD.
PubMed: 38934044
DOI: 10.23876/j.krcp.23.287 -
Kidney Research and Clinical Practice May 2024The global coronavirus disease 2019 (COVID-19) pandemic has placed patients with end-stage kidney disease (ESKD) at heightened risk owing to their vulnerability to...
BACKGROUND
The global coronavirus disease 2019 (COVID-19) pandemic has placed patients with end-stage kidney disease (ESKD) at heightened risk owing to their vulnerability to infections. Our study focused on patients with ESKD, examining COVID-19 incidence, hospitalization, and mortality in relation to their renal replacement therapy (RRT) type and identifying factors influencing COVID-19 hospitalization.
METHODS
We conducted a retrospective cohort study using health insurance claims data from the Health Insurance Review and Assessment Service for patients with ESKD between July 2017 and June 2022. COVID-19 data for the general population were sourced from the Korea Disease Control and Prevention Agency.
RESULTS
Patients undergoing hemodialysis (HD) constituted 90.7% of the cohort, followed by kidney transplantation (KT) recipients and peritoneal dialysis (PD). After adjusting for every 10,000 individuals, KT recipients exhibited the highest COVID-19 incidence, followed by those undergoing HD and PD, whereas the general population showed a higher infection rate of 43.64. Patients undergoing HD had the highest hospitalization rates, followed by KT recipients and those undergoing PD. The mortality rate per 10,000 individuals was highest in HD, followed by PD, the general population, and KT. Multivariate analysis indicated that age, RRT duration, residence in a nursing hospital, and comorbidities were associated with COVID-19 hospitalization.
CONCLUSION
Among RRT modalities, KT recipients displayed the highest COVID-19 incidence, whereas those undergoing HD exhibited the highest hospitalization and mortality rates. This study contributes to our understanding of infectious diseases in patients on RRT and aids in preparedness for future infectious disease outbreaks.
PubMed: 38934043
DOI: 10.23876/j.krcp.23.280 -
Microorganisms Jun 2024Sulforaphane (SFN) is a natural isothiocyanate derived from cruciferous vegetables such as broccoli, Brussels sprouts, and cabbage. SFN plays a crucial role in...
Sulforaphane (SFN) is a natural isothiocyanate derived from cruciferous vegetables such as broccoli, Brussels sprouts, and cabbage. SFN plays a crucial role in maintaining redox homeostasis by interacting with the active cysteine residues of Keap1, leading to the dissociation and activation of NRF2 in various diseases. In this study, our objective was to investigate the impact of SFN on oxidative stress and pyroptosis in ()-infected macrophages. Our findings demonstrated that infection significantly increased the production of iNOS and ROS, indicating the induction of oxidative stress in macrophages. However, treatment with SFN effectively suppressed the expression of iNOS and COX-2 and reduced MDA and ROS levels, while enhancing GSH content as well as upregulating NRF2, HO-1, and NQO-1 expression in -infected RAW264.7 macrophages and primary peritoneal macrophages from WT mice. These results suggest that SFN mitigates oxidative stress by activating the NRF2 signaling pathway in -infected macrophages. Furthermore, excessive ROS production activates the NLRP3 signaling pathway, thereby promoting pyroptosis onset. Further investigations revealed that SFN effectively suppressed the expression of NLRP3, Caspase-1, and GSDMD, IL-1β, and IL-18 levels, as well as the production of LDH, suggesting that it may exhibit anti-pyroptotic effects through activation of the NRF2 signaling pathway and reductions in ROS production during infection. Moreover, we observed that SFN also inhibited the expression of NLRP3, ASC, Caspase1, and IL-1β along with LDH production in -infected primary peritoneal macrophages from NFR2 mice. This indicates that SFN can directly suppress NLRP3 activation and possibly inhibit pyroptosis initiation in an NRF2-independent manner. In summary, our findings demonstrate that SFN exerts its inhibitory effects on oxidative stress by activating the NRF2 signaling pathway in -infected macrophages, while it may simultaneously exert anti-pyroptotic properties through both NRF2-dependent and independent mechanisms targeting the NLRP3 signaling pathway.
PubMed: 38930573
DOI: 10.3390/microorganisms12061191 -
Microorganisms May 2024Leptospirosis is an infectious disease that affects domestic animals, wild animals, and humans. It represents a public health problem and has an important economic...
Leptospirosis is an infectious disease that affects domestic animals, wild animals, and humans. It represents a public health problem and has an important economic impact on livestock. This study aims to investigate the importance of genital and transplacental infection in the epidemiology of leptospirosis in cows maintained in Caatinga biome conditions, Northeastern Brazil, as well as reporting organs colonized by spp. in embryos and fetuses. Blood, urinary tract (urine, bladder, and kidney), and reproductive tract (vaginal fluid, uterus, uterine tube, ovary, and placenta) samples were collected from 15 slaughtered pregnant cows. Two embryos and 13 fetuses were sampled. Central nervous system and choroid ovoid samples were collected from embryos. Blood, central nervous system, lung, peritoneal liquid, abomasal content, liver, spleen, urine, bladder, kidney, and reproductive system samples were collected from fetuses. Diagnostic methods included the microscopic agglutination test (MAT) using a collection of 24 serovars belonging to 17 different pathogenic serogroups of five species as antigens, as well as polymerase chain reaction (PCR). Anti- spp. antibodies were found in 9 cows (60%), while 13 cows (86.67%) had at least one organ or urine with leptospiral DNA. No fetus was seroreactive. Among the embryos and fetuses, 13 (86.67%) presented leptospiral DNA, proving a high frequency of transplacental infection (100%). For cows, the most frequent biological materials regarding spp. DNA detection were placenta (13 out of 15 samples; 86.7%), uterus (10 out of 15 samples; 66.7%), and vaginal fluid (5 out of 15 samples; 33.3%), while, for fetuses/embryos, the most frequent PCR-positive samples were choroid ovoid (1/2; 50%), spleen (6/13; 46.2%), kidney (5/13; 38.5%), and central nervous system (5/15; 33.3%). Sequenced samples based on the LipL32 gene presented 99% similarity with . The results indicate that transplacental infection is an efficient way of spreading spp. in cows maintained in Caatinga biome conditions. Therefore, prevention and control strategies must include actions that interrupt transmission through this alternative route.
PubMed: 38930426
DOI: 10.3390/microorganisms12061044 -
Antibiotics (Basel, Switzerland) Jun 2024is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, is the only... (Review)
Review
is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, is the only species of its genus. It was first isolated in 2003 during a study into the flora of lagoons and manure pits. Given the rarity of this microorganism and the sparse information in the literature about its way of transmission, the way to diagnose its infections and identify it in the microbiology laboratory, and its public health relevance, the present study aimed to identify all the published cases of , describe the epidemiological, clinical, and microbiological characteristics, and provide information about its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a Pubmed/Medline and Scopus databases search. In total, 14 studies provided data on 17 patients with infections by . The median age of patients was 63 years and 47% were male. The most common types of infection were bone and joint infections, bacteremia, infective endocarditis, and peritonitis. The only isolated species was , and antimicrobial resistance to clindamycin was 50%, but was 0% to the combination of piperacillin with tazobactam, aminopenicillin with a beta-lactamase inhibitor, and metronidazole which were the most commonly used antimicrobials for the treatment of these infections. The overall mortality depends on the type of infection and is notable only for bacteremia, while all other infections had an optimal outcome. Future studies should better assess these infections' clinical and epidemiological characteristics and the mechanisms of the antimicrobial resistance of this microorganism from a mechanistic and genetic perspective.
PubMed: 38927236
DOI: 10.3390/antibiotics13060570 -
Antibiotics (Basel, Switzerland) Jun 2024species (formerly known as ) are Gram-positive filamentous bacteria in the family Promicromonosporaceae and are more commonly found in sewage and soil. The present... (Review)
Review
species (formerly known as ) are Gram-positive filamentous bacteria in the family Promicromonosporaceae and are more commonly found in sewage and soil. The present study aimed to identify all the published cases of species infections in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus database search. In total, 38 studies provided data on 40 patients with infections by these species. The median age of patients was 52.5 years, and 55% were male. The most common infection types were bacteremia, infective endocarditis (IE), osteoarticular infections, peritoneal dialysis-associated peritonitis, and endophthalmitis. Antimicrobial resistance to vancomycin and the combination of trimethoprim and sulfamethoxazole was minimal, and vancomycin was the most commonly used antimicrobial for treating these infections. Overall mortality was minimal for all infections, except for bacteremia and IE, which carried high mortality rates.
PubMed: 38927228
DOI: 10.3390/antibiotics13060562 -
Antibiotics (Basel, Switzerland) Jun 2024is a Gram-negative rod that belongs to the order Enterobacterales and the family Yersiniaceae and was first identified in 1983 from 10 clinical strains in the United... (Review)
Review
is a Gram-negative rod that belongs to the order Enterobacterales and the family Yersiniaceae and was first identified in 1983 from 10 clinical strains in the United States of America. The present study aimed to identify all the published cases of in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus databases search. In total, 16 studies provided data on 19 patients with infections by . The median age of the patients was 55 years, and 47.4% were male. The most common infections were those of the bloodstream, the respiratory tract, and the peritoneal cavity. Antimicrobial resistance to cephalosporins, aminoglycosides, and the combination of trimethoprim with sulfamethoxazole was minimal, and these were the most commonly used antimicrobials for treating these infections. No included study provided information on the genetic or molecular mechanism of this pathogen's antimicrobial resistance. The overall mortality was minimal, with only one patient with bacteremia succumbing to the infection. Further studies are needed to better understand this microorganism, its pathogenic potential in humans, and the genetic and molecular mechanisms underlying its antimicrobial resistance, for which very little evidence exists to date.
PubMed: 38927225
DOI: 10.3390/antibiotics13060559 -
Indian Journal of Medical Microbiology Jun 2024The Aeromonadaceae family, comprised of gram-negative bacilli, is ubiquitously distributed across the globe. Infections by Aeromonas species encompass gastroenteritis,...
The Aeromonadaceae family, comprised of gram-negative bacilli, is ubiquitously distributed across the globe. Infections by Aeromonas species encompass gastroenteritis, septicaemia, skin and soft tissue infections (SSTIs), pneumonia, and peritonitis. This report delineates a case of Aeromonas hydrophila infection, manifesting as an array of pustules on the patient's lower extremities subsequent to the ingestion of marine crustaceans, specifically prawns. Prompt diagnosis and the initiation of an appropriate antibiotic regimen are imperative to mitigate the risk of further complications.
PubMed: 38925279
DOI: 10.1016/j.ijmmb.2024.100658