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Frontiers in Immunology 2019In primary infection with , it has been reported-without consideration of 's functions-that humoral immunity plays no role in the clearance of bacteria. In fact,... (Review)
Review
In primary infection with , it has been reported-without consideration of 's functions-that humoral immunity plays no role in the clearance of bacteria. In fact, targets and suppresses several aspects of humoral immunity, including B cell lymphopoiesis, B cell activation, and IgG production. In particular, the suppression of IgG-secreting plasma cell maintenance allows the persistence of in tissues. Therefore, the critical role(s) of humoral immunity in the response to infection, especially at the late phase, should be re-investigated. The suppression of IgG plasma cell memory strongly hinders vaccine development against non-typhoidal (NTS) because can also reduce humoral immune memory against other bacteria and viruses, obtained from previous vaccination or infection. We propose a new vaccine against that would not impair humoral immunity, and which could also be used as a treatment for antibody-dependent autoimmune diseases to deplete pathogenic long-lived plasma cells, by utilizing the 's own suppression mechanism of humoral immunity.
Topics: Animals; B-Lymphocytes; Host-Pathogen Interactions; Humans; Immunity, Humoral; Plasma Cells; Salmonella; Salmonella Infections
PubMed: 32038650
DOI: 10.3389/fimmu.2019.03155 -
Microbiology (Reading, England) Nov 2018Global Salmonella infection, especially in developing countries, is a health and economic burden. The use of antibiotic drugs in treating the infection is proving less... (Review)
Review
Global Salmonella infection, especially in developing countries, is a health and economic burden. The use of antibiotic drugs in treating the infection is proving less effective due to the alarming rise of antibiotic-resistant strains of Salmonella, the effects of antibiotics on normal gut microflora and antibiotic-associated diarrhoea, all of which bring a growing need for alternative treatments, including the use of probiotic micro-organisms. However, there are issues with probiotics, including their potential to be opportunistic pathogens and antibiotic-resistant carriers, and their antibiotic susceptibility if used as complementary therapy. Clinical trials, animal trials and in vitro investigations into the prophylactic and therapeutic efficacies of probiotics have demonstrated antagonistic properties against Salmonella and other enteropathogenic bacteria. Nonetheless, there is a need for further studies into the potential mechanisms, efficacy and mode of delivery of yeast probiotics in Salmonella infections. This review discusses Salmonella infections and treatment using antibiotics and probiotics.
Topics: Anti-Bacterial Agents; Biofilms; Drug Resistance, Multiple, Bacterial; Gastrointestinal Microbiome; Humans; Probiotics; Salmonella; Salmonella Infections
PubMed: 30136920
DOI: 10.1099/mic.0.000709 -
Immunology Letters Oct 2017Salmonella infection causes morbidity and mortality throughout the world with the host immune response varying depending on whether the infection is acute and limited,... (Review)
Review
Salmonella infection causes morbidity and mortality throughout the world with the host immune response varying depending on whether the infection is acute and limited, or systemic and chronic. Additionally, Salmonella bacteria have evolved multiple mechanisms to avoid or subvert immunity to its own benefit and often the anatomical location of infection plays a role in both the immune response and bacterial fate. Here, we provide an overview of the interplay between the immune system and Salmonella, while discussing how different host and bacterial factors influence the outcome of infection.
Topics: Adaptive Immunity; Animals; Host-Pathogen Interactions; Humans; Immune System; Immunity, Innate; Immunomodulation; Salmonella; Salmonella Infections; Salmonella Infections, Animal
PubMed: 28720334
DOI: 10.1016/j.imlet.2017.07.006 -
Clinical Microbiology Reviews Jan 2019The ability of pathogenic bacteria to affect higher organisms and cause disease is one of the most dramatic properties of microorganisms. Some pathogens can establish... (Review)
Review
The ability of pathogenic bacteria to affect higher organisms and cause disease is one of the most dramatic properties of microorganisms. Some pathogens can establish transient colonization only, but others are capable of infecting their host for many years or even for a lifetime. Long-term infection is called persistence, and this phenotype is fundamental for the biology of important human pathogens, including , , and Both typhoidal and nontyphoidal serovars of the species can cause persistent infection in humans; however, as these two groups cause clinically distinct diseases, the characteristics of their persistent infections in humans differ significantly. Here, following a general summary of pathogenicity, host specificity, epidemiology, and laboratory diagnosis, I review the current knowledge about persistence and discuss the relevant epidemiology of persistence (including carrier rate, duration of shedding, and host and pathogen risk factors), the host response to persistence, genes involved in this lifestyle, as well as genetic and phenotypic changes acquired during prolonged infection within the host. Additionally, I highlight differences between the persistence of typhoidal and nontyphoidal strains in humans and summarize the current gaps and limitations in our understanding, diagnosis, and curing of persistent infections.
Topics: Carrier State; Humans; Risk Factors; Salmonella Infections; Salmonella enterica; Serogroup
PubMed: 30487167
DOI: 10.1128/CMR.00088-18 -
Clinical Microbiology Reviews Oct 2015Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses... (Review)
Review
Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Salmonella; Salmonella Infections
PubMed: 26180063
DOI: 10.1128/CMR.00002-15 -
The Lancet. Infectious Diseases Dec 2019Non-typhoidal salmonella invasive disease is a major cause of global morbidity and mortality. Malnourished children, those with recent malaria or sickle-cell anaemia,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-typhoidal salmonella invasive disease is a major cause of global morbidity and mortality. Malnourished children, those with recent malaria or sickle-cell anaemia, and adults with HIV infection are at particularly high risk of disease. We sought to estimate the burden of disease attributable to non-typhoidal salmonella invasive disease for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017.
METHODS
We did a systematic review of scientific databases and grey literature, and estimated non-typhoidal salmonella invasive disease incidence and mortality for the years 1990 to 2017, by age, sex, and geographical location using DisMod-MR, a Bayesian meta-regression tool. We estimated case fatality by age, HIV status, and sociodemographic development. We also calculated the HIV-attributable fraction and estimated health gap metrics, including disability-adjusted life-years (DALYs).
FINDINGS
We estimated that 535 000 (95% uncertainty interval 409 000-705 000) cases of non-typhoidal salmonella invasive disease occurred in 2017, with the highest incidence in sub-Saharan Africa (34·5 [26·6-45·0] cases per 100 000 person-years) and in children younger than 5 years (34·3 [23·2-54·7] cases per 100 000 person-years). 77 500 (46 400-123 000) deaths were estimated in 2017, of which 18 400 (12 000-27 700) were attributable to HIV. The remaining 59 100 (33 300-98 100) deaths not attributable to HIV accounted for 4·26 million (2·38-7·38) DALYs in 2017. Mean all-age case fatality was 14·5% (9·2-21·1), with higher estimates among children younger than 5 years (13·5% [8·4-19·8]) and elderly people (51·2% [30·2-72·9] among those aged ≥70 years), people with HIV infection (41·8% [30·0-54·0]), and in areas of low sociodemographic development (eg, 15·8% [10·0-22·9] in sub-Saharan Africa).
INTERPRETATION
We present the first global estimates of non-typhoidal salmonella invasive disease that have been produced as part of GBD 2017. Given the high disease burden, particularly in children, elderly people, and people with HIV infection, investigating the sources and transmission pathways of non-typhoidal salmonella invasive disease is crucial to implement effective preventive and control measures.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Female; Geography, Medical; Global Burden of Disease; Humans; Incidence; Male; Prevalence; Risk Factors; Salmonella; Salmonella Infections; Socioeconomic Factors
PubMed: 31562022
DOI: 10.1016/S1473-3099(19)30418-9 -
Science (New York, N.Y.) Jul 2020The guanosine triphosphatase (GTPase) Rab32 coordinates a cell-intrinsic host defense mechanism that restricts the replication of intravacuolar pathogens such as Here,...
The guanosine triphosphatase (GTPase) Rab32 coordinates a cell-intrinsic host defense mechanism that restricts the replication of intravacuolar pathogens such as Here, we show that this mechanism requires aconitate decarboxylase 1 (IRG1), which synthesizes itaconate, a metabolite with antimicrobial activity. We find that Rab32 interacts with IRG1 on infection and facilitates the delivery of itaconate to the -containing vacuole. Mice defective in IRG1 rescued the virulence defect of a serovar Typhimurium mutant specifically defective in its ability to counter the Rab32 defense mechanism. These studies provide a link between a metabolite produced in the mitochondria after stimulation of innate immune receptors and a cell-autonomous defense mechanism that restricts the replication of an intracellular bacterial pathogen.
Topics: Animals; Cell Line; Host-Pathogen Interactions; Humans; Hydro-Lyases; Mice; Salmonella Infections; Salmonella enterica; Salmonella typhimurium; Succinates; Virulence; rab GTP-Binding Proteins
PubMed: 32703879
DOI: 10.1126/science.aaz1333 -
Frontiers in Cellular and Infection... 2018are facultative intracellular pathogens that cause globally distributed diseases with massive morbidity and mortality in humans and animals. In the past decades,... (Review)
Review
are facultative intracellular pathogens that cause globally distributed diseases with massive morbidity and mortality in humans and animals. In the past decades, numerous studies were focused on host defenses against infection. Autophagy has been demonstrated to be an important defense mechanism to clear intracellular pathogenic organisms, as well as a regulator of immune responses. Ubiquitin modification also has multiple effects on the host immune system against bacterial infection. It has been indicated that ubiquitination plays critical roles in recognition and clearance of some invading bacteria by autophagy. Additionally, the ubiquitination of autophagy proteins in autophagy flux and inflammation-related substance determines the outcomes of infection. However, many intracellular pathogens manipulate the ubiquitination system to counteract the host immunity. interfere with host responses via the delivery of ~30 effector proteins into cytosol to promote their survival and proliferation. Among them, some could link the ubiquitin-proteasome system with autophagy during infection and affect the host inflammatory responses. In this review, novel findings on the issue of ubiquitination and autophagy connection as the mechanisms of host defenses against infection and the subverted processes are introduced.
Topics: Animals; Autophagy; Bacterial Proteins; Host-Pathogen Interactions; Humans; Salmonella Infections; Salmonella typhimurium; Ubiquitination
PubMed: 29594070
DOI: 10.3389/fcimb.2018.00078 -
Frontiers in Cellular and Infection... 2018are Gram-negative rod-shaped facultative anaerobic bacteria that are comprised of over 2,000 serovars. They cause gastroenteritis (salmonellosis) with headache,... (Review)
Review
are Gram-negative rod-shaped facultative anaerobic bacteria that are comprised of over 2,000 serovars. They cause gastroenteritis (salmonellosis) with headache, abdominal pain and diarrhea clinical symptoms. Salmonellosis brings a heavy burden for the public health in both developing and developed countries. Antibiotics are usually effective in treating the infected patients with severe gastroenteritis, although antibiotic resistance is on the rise. Understanding the molecular mechanisms of infection is vital to combat the disease. immortalized 2-D cell lines, tissues/organs and several animal models have been successfully utilized to study infections. Although these infection models have contributed to uncovering the molecular virulence mechanisms, some intrinsic shortcomings have limited their wider applications. Notably, cell lines only contain a single cell type, which cannot reproduce some of the hallmarks of natural infections. While tissues/organs alleviate some of these concerns, they are more difficult to maintain, in particular for long term experiments. In addition, non-human animal models are known to reflect only part of the human disease process. Enteroids and induced intestinal organoids are emerging as effective infection models due to their closeness in mimicking the infected tissues/organs. Induced intestinal organoids are derived from iPSCs and contain mesenchymal cells whereas enteroids are derive from intestinal stem cells and are comprised of epithelial cells only. Both enteroids and induced intestinal organoids mimic the villus and crypt domains comparable to the architectures of the intestine. We review here that enteroids and induced intestinal organoids are emerging as desired infection models to study bacterial-host interactions of .
Topics: Animals; Humans; Intestinal Mucosa; Macrophages; Mice; Organoids; Salmonella; Salmonella Infections; Virulence Factors
PubMed: 29670862
DOI: 10.3389/fcimb.2018.00102 -
Molecular and Cellular Endocrinology Aug 2017The Janus kinase/signal transducers and activators for transcription (JAK/STAT) pathway plays crucial roles in regulating apoptosis, proliferation, differentiation, and... (Review)
Review
The Janus kinase/signal transducers and activators for transcription (JAK/STAT) pathway plays crucial roles in regulating apoptosis, proliferation, differentiation, and the inflammatory response. The JAK/STAT families are composed of four JAK family members and seven STAT family members. STAT3 plays a key role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment. Recent evidence suggests that STAT3 regulates diverse biological functions in pathogenesis of diseases, such as infection and cancer. In the current review, we will summarize the research progress of STAT3 activation in infection and cancers. We highlight our recent study on the novel role of STAT3 in Salmonella infection-associated colon cancer. Infection with bacterial AvrA-expressing Salmonella activates the STAT3 pathway, which induces the β-catenin signals and enhances colonic tumorigenesis. STAT3 may be a promising target in developing prevention and treatment for infectious diseases and infection-associated cancers.
Topics: Apoptosis; Bacterial Proteins; Carcinogenesis; Cell Proliferation; Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Host-Pathogen Interactions; Humans; Janus Kinase 2; STAT3 Transcription Factor; Salmonella; Salmonella Infections; Signal Transduction; beta Catenin
PubMed: 28223148
DOI: 10.1016/j.mce.2017.02.023